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1917307 | Confirmatory | Antiproliferative activity against human U-251 cells measured after 48 hrs by MTT assay | Title: Discovery of polymethoxyphenyl-pyridines bearing amino side chains as tubulin colchicine-binding site inhibitors._||_Abstract: Nineteen TH03 analogues were designed and synthesized as tubulin colchicine-binding site inhibitors with potent antiproliferative activities. Among these compounds, 3,5-dimethoxyphenylpyridines 8j bearing a 4-methoxybenzyl aniline side-chain displayed the best antiproliferative activities against glioma (U87MG and U251). In addition, the trimethoxyphenylpyridine 8o bearing a 4-methyl-N-methyl aniline side-chain showed the best antiproliferative activities against colon carcinoma and lung cancer with the lowest IC<sub>50</sub> value (0.09 µM < IC<sub>50</sub> < 0.86 µM). Compared with CA-4, Compounds 8j and 8o displayed lower cytotoxicities toward normal cells but higher antiproliferative activities against RKO (IC<sub>50</sub> = 0.15 µM and 0.09 µM respectively), NCI-H1299 (IC<sub>50</sub> = 0.73 µM and 0.14 µM respectively), and A549 cells (IC<sub>50</sub> = 0.86 µM and 0.37 µM respectively). Further investigations revealed that 8o shows higher tubulin polymerization inhibitory activity (IC<sub>50</sub> = 3.1 ± 0.5 µM) than colchicine (IC<sub>50</sub> = 8.6 ± 0.2 µM), and induced cell cycle arrest at the G2/M phase and cellular apoptosis through disrupting the microtubule network. | Compounds with activity <= 10uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation._||_Journal: Bioorg Med Chem_||_Year: 2022_||_Volume: 73_||_First Page: 117007_||_Last Page: 117007_||_DOI: 10.1016/j.bmc.2022.117007_||_Target ChEMBL ID: CHEMBL615022_||_ChEMBL Target Name: U-251_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5216829 | 20230629 | 20230629 | 5351344|156019791|164623302|168298105|168298133|168298155|168298284|168298403|168298477|168298491|168298505|168298550|168298650|168298857|168298859|168299039|168299457|168299486|168299499|168299520|168299646|168299820 | 103168561|442060974|469818531|482088488|482088525|482088558|482088741|482088909|482089005|482089025|482089044|482089105|482089237|482089528|482089530|482089777|482090357|482090393|482090411|482090437|482090621|482090864 | null | null | null | Curation Efforts|Research and Development | 36150341 | 0 | null | null | 9606 | null | null | 22 | 7 | null | null | null |
1917308 | Confirmatory | Antiproliferative activity against human SH-SY5Y cells measured after 48 hrs by MTT assay | Title: Discovery of polymethoxyphenyl-pyridines bearing amino side chains as tubulin colchicine-binding site inhibitors._||_Abstract: Nineteen TH03 analogues were designed and synthesized as tubulin colchicine-binding site inhibitors with potent antiproliferative activities. Among these compounds, 3,5-dimethoxyphenylpyridines 8j bearing a 4-methoxybenzyl aniline side-chain displayed the best antiproliferative activities against glioma (U87MG and U251). In addition, the trimethoxyphenylpyridine 8o bearing a 4-methyl-N-methyl aniline side-chain showed the best antiproliferative activities against colon carcinoma and lung cancer with the lowest IC<sub>50</sub> value (0.09 µM < IC<sub>50</sub> < 0.86 µM). Compared with CA-4, Compounds 8j and 8o displayed lower cytotoxicities toward normal cells but higher antiproliferative activities against RKO (IC<sub>50</sub> = 0.15 µM and 0.09 µM respectively), NCI-H1299 (IC<sub>50</sub> = 0.73 µM and 0.14 µM respectively), and A549 cells (IC<sub>50</sub> = 0.86 µM and 0.37 µM respectively). Further investigations revealed that 8o shows higher tubulin polymerization inhibitory activity (IC<sub>50</sub> = 3.1 ± 0.5 µM) than colchicine (IC<sub>50</sub> = 8.6 ± 0.2 µM), and induced cell cycle arrest at the G2/M phase and cellular apoptosis through disrupting the microtubule network. | Compounds with activity <= 10uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation._||_Journal: Bioorg Med Chem_||_Year: 2022_||_Volume: 73_||_First Page: 117007_||_Last Page: 117007_||_DOI: 10.1016/j.bmc.2022.117007_||_Target ChEMBL ID: CHEMBL614910_||_ChEMBL Target Name: SH-SY5Y_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5216830 | 20230629 | 20230629 | 145954499 | 404659184 | null | null | null | Curation Efforts|Research and Development | 36150341 | 0 | null | null | 9606 | null | null | 1 | 1 | null | null | null |
1917309 | Confirmatory | Inhibition of PDE4 CAT (unknown origin) | Title: Discovery of polymethoxyphenyl-pyridines bearing amino side chains as tubulin colchicine-binding site inhibitors._||_Abstract: Nineteen TH03 analogues were designed and synthesized as tubulin colchicine-binding site inhibitors with potent antiproliferative activities. Among these compounds, 3,5-dimethoxyphenylpyridines 8j bearing a 4-methoxybenzyl aniline side-chain displayed the best antiproliferative activities against glioma (U87MG and U251). In addition, the trimethoxyphenylpyridine 8o bearing a 4-methyl-N-methyl aniline side-chain showed the best antiproliferative activities against colon carcinoma and lung cancer with the lowest IC<sub>50</sub> value (0.09 µM < IC<sub>50</sub> < 0.86 µM). Compared with CA-4, Compounds 8j and 8o displayed lower cytotoxicities toward normal cells but higher antiproliferative activities against RKO (IC<sub>50</sub> = 0.15 µM and 0.09 µM respectively), NCI-H1299 (IC<sub>50</sub> = 0.73 µM and 0.14 µM respectively), and A549 cells (IC<sub>50</sub> = 0.86 µM and 0.37 µM respectively). Further investigations revealed that 8o shows higher tubulin polymerization inhibitory activity (IC<sub>50</sub> = 3.1 ± 0.5 µM) than colchicine (IC<sub>50</sub> = 8.6 ± 0.2 µM), and induced cell cycle arrest at the G2/M phase and cellular apoptosis through disrupting the microtubule network. | Compounds with activity <= 10uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation._||_Journal: Bioorg Med Chem_||_Year: 2022_||_Volume: 73_||_First Page: 117007_||_Last Page: 117007_||_DOI: 10.1016/j.bmc.2022.117007_||_Target ChEMBL ID: CHEMBL291_||_ChEMBL Target Name: Phosphodiesterase 4C_||_ChEMBL Target Type: SINGLE PROTEIN - Target is a single protein chain_||_Relationship Type: D - Direct protein target assigned_||_Confidence: Direct single protein target assigned | 43 | ChEMBL | CHEMBL5216831 | 20230629 | 20230629 | 164623302 | 469818531 | 5143 | null | Q08493 | Curation Efforts|Research and Development | 36150341 | 0 | 3.1.4.53 | Q08493 | 9606 | null | null | 1 | 1 | null | null | null |
1917310 | Literature-derived | Inhibition of pig brain tubulin polymerization at 10 uM by spectrometric method relative to control | Title: Discovery of polymethoxyphenyl-pyridines bearing amino side chains as tubulin colchicine-binding site inhibitors._||_Abstract: Nineteen TH03 analogues were designed and synthesized as tubulin colchicine-binding site inhibitors with potent antiproliferative activities. Among these compounds, 3,5-dimethoxyphenylpyridines 8j bearing a 4-methoxybenzyl aniline side-chain displayed the best antiproliferative activities against glioma (U87MG and U251). In addition, the trimethoxyphenylpyridine 8o bearing a 4-methyl-N-methyl aniline side-chain showed the best antiproliferative activities against colon carcinoma and lung cancer with the lowest IC<sub>50</sub> value (0.09 µM < IC<sub>50</sub> < 0.86 µM). Compared with CA-4, Compounds 8j and 8o displayed lower cytotoxicities toward normal cells but higher antiproliferative activities against RKO (IC<sub>50</sub> = 0.15 µM and 0.09 µM respectively), NCI-H1299 (IC<sub>50</sub> = 0.73 µM and 0.14 µM respectively), and A549 cells (IC<sub>50</sub> = 0.86 µM and 0.37 µM respectively). Further investigations revealed that 8o shows higher tubulin polymerization inhibitory activity (IC<sub>50</sub> = 3.1 ± 0.5 µM) than colchicine (IC<sub>50</sub> = 8.6 ± 0.2 µM), and induced cell cycle arrest at the G2/M phase and cellular apoptosis through disrupting the microtubule network. | Journal: Bioorg Med Chem_||_Year: 2022_||_Volume: 73_||_First Page: 117007_||_Last Page: 117007_||_DOI: 10.1016/j.bmc.2022.117007_||_Target ChEMBL ID: CHEMBL2111354_||_ChEMBL Target Name: Tubulin_||_ChEMBL Target Type: PROTEIN FAMILY - Target is a group of closely related proteins_||_Relationship Type: D - Direct protein target assigned_||_Confidence: Multiple direct protein targets may be assigned | 43 | ChEMBL | CHEMBL5216832 | 20230629 | 20230629 | 6167|5351344|156019791|164623302|168298477|168299486|168299520 | 103168561|103177124|442060974|469818531|482089005|482090393|482090437 | 100135051 | null | P02550|P02554 | Curation Efforts|Research and Development | 36150341 | 0 | 3.6.5.- | P02550|P02554 | 9823 | null | null | 7 | null | null | null | null |
1917311 | Confirmatory | Inhibition of pig brain tubulin polymerization by spectrometric method | Title: Discovery of polymethoxyphenyl-pyridines bearing amino side chains as tubulin colchicine-binding site inhibitors._||_Abstract: Nineteen TH03 analogues were designed and synthesized as tubulin colchicine-binding site inhibitors with potent antiproliferative activities. Among these compounds, 3,5-dimethoxyphenylpyridines 8j bearing a 4-methoxybenzyl aniline side-chain displayed the best antiproliferative activities against glioma (U87MG and U251). In addition, the trimethoxyphenylpyridine 8o bearing a 4-methyl-N-methyl aniline side-chain showed the best antiproliferative activities against colon carcinoma and lung cancer with the lowest IC<sub>50</sub> value (0.09 µM < IC<sub>50</sub> < 0.86 µM). Compared with CA-4, Compounds 8j and 8o displayed lower cytotoxicities toward normal cells but higher antiproliferative activities against RKO (IC<sub>50</sub> = 0.15 µM and 0.09 µM respectively), NCI-H1299 (IC<sub>50</sub> = 0.73 µM and 0.14 µM respectively), and A549 cells (IC<sub>50</sub> = 0.86 µM and 0.37 µM respectively). Further investigations revealed that 8o shows higher tubulin polymerization inhibitory activity (IC<sub>50</sub> = 3.1 ± 0.5 µM) than colchicine (IC<sub>50</sub> = 8.6 ± 0.2 µM), and induced cell cycle arrest at the G2/M phase and cellular apoptosis through disrupting the microtubule network. | Compounds with activity <= 10uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation._||_Journal: Bioorg Med Chem_||_Year: 2022_||_Volume: 73_||_First Page: 117007_||_Last Page: 117007_||_DOI: 10.1016/j.bmc.2022.117007_||_Target ChEMBL ID: CHEMBL2111354_||_ChEMBL Target Name: Tubulin_||_ChEMBL Target Type: PROTEIN FAMILY - Target is a group of closely related proteins_||_Relationship Type: D - Direct protein target assigned_||_Confidence: Multiple direct protein targets may be assigned | 43 | ChEMBL | CHEMBL5216833 | 20230629 | 20230629 | 6167|5351344|145954499|156019791|168298477|168299486|168299520 | 103168561|103177124|404659184|442060974|482089005|482090393|482090437 | 100135051 | null | P02550|P02554 | Curation Efforts|Research and Development | 36150341 | 0 | 3.6.5.- | P02550|P02554 | 9823 | null | null | 7 | 6 | null | null | null |
1917312 | Confirmatory | Cytotoxicity against mouse HT-22 cells measured after 48 hrs by MTT assay | Title: Discovery of polymethoxyphenyl-pyridines bearing amino side chains as tubulin colchicine-binding site inhibitors._||_Abstract: Nineteen TH03 analogues were designed and synthesized as tubulin colchicine-binding site inhibitors with potent antiproliferative activities. Among these compounds, 3,5-dimethoxyphenylpyridines 8j bearing a 4-methoxybenzyl aniline side-chain displayed the best antiproliferative activities against glioma (U87MG and U251). In addition, the trimethoxyphenylpyridine 8o bearing a 4-methyl-N-methyl aniline side-chain showed the best antiproliferative activities against colon carcinoma and lung cancer with the lowest IC<sub>50</sub> value (0.09 µM < IC<sub>50</sub> < 0.86 µM). Compared with CA-4, Compounds 8j and 8o displayed lower cytotoxicities toward normal cells but higher antiproliferative activities against RKO (IC<sub>50</sub> = 0.15 µM and 0.09 µM respectively), NCI-H1299 (IC<sub>50</sub> = 0.73 µM and 0.14 µM respectively), and A549 cells (IC<sub>50</sub> = 0.86 µM and 0.37 µM respectively). Further investigations revealed that 8o shows higher tubulin polymerization inhibitory activity (IC<sub>50</sub> = 3.1 ± 0.5 µM) than colchicine (IC<sub>50</sub> = 8.6 ± 0.2 µM), and induced cell cycle arrest at the G2/M phase and cellular apoptosis through disrupting the microtubule network. | Journal: Bioorg Med Chem_||_Year: 2022_||_Volume: 73_||_First Page: 117007_||_Last Page: 117007_||_DOI: 10.1016/j.bmc.2022.117007_||_Target ChEMBL ID: CHEMBL614316_||_ChEMBL Target Name: HT-22_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5216834 | 20230629 | 20230629 | 6167|5351344|156019791|168298477|168299486|168299520 | 103168561|103177124|442060974|482089005|482090393|482090437 | null | Toxicity | null | Curation Efforts|Research and Development | 36150341 | 0 | null | null | 10090 | null | null | 6 | null | null | null | null |
1917313 | Confirmatory | Cytotoxicity against human NCM460 cells measured after 48 hrs by MTT assay | Title: Discovery of polymethoxyphenyl-pyridines bearing amino side chains as tubulin colchicine-binding site inhibitors._||_Abstract: Nineteen TH03 analogues were designed and synthesized as tubulin colchicine-binding site inhibitors with potent antiproliferative activities. Among these compounds, 3,5-dimethoxyphenylpyridines 8j bearing a 4-methoxybenzyl aniline side-chain displayed the best antiproliferative activities against glioma (U87MG and U251). In addition, the trimethoxyphenylpyridine 8o bearing a 4-methyl-N-methyl aniline side-chain showed the best antiproliferative activities against colon carcinoma and lung cancer with the lowest IC<sub>50</sub> value (0.09 µM < IC<sub>50</sub> < 0.86 µM). Compared with CA-4, Compounds 8j and 8o displayed lower cytotoxicities toward normal cells but higher antiproliferative activities against RKO (IC<sub>50</sub> = 0.15 µM and 0.09 µM respectively), NCI-H1299 (IC<sub>50</sub> = 0.73 µM and 0.14 µM respectively), and A549 cells (IC<sub>50</sub> = 0.86 µM and 0.37 µM respectively). Further investigations revealed that 8o shows higher tubulin polymerization inhibitory activity (IC<sub>50</sub> = 3.1 ± 0.5 µM) than colchicine (IC<sub>50</sub> = 8.6 ± 0.2 µM), and induced cell cycle arrest at the G2/M phase and cellular apoptosis through disrupting the microtubule network. | Compounds with activity <= 10uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation._||_Journal: Bioorg Med Chem_||_Year: 2022_||_Volume: 73_||_First Page: 117007_||_Last Page: 117007_||_DOI: 10.1016/j.bmc.2022.117007_||_Target ChEMBL ID: CHEMBL4483264_||_ChEMBL Target Name: NCM460_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5216835 | 20230629 | 20230629 | 6167|5351344|156019791|168298477|168299486|168299520 | 103168561|103177124|442060974|482089005|482090393|482090437 | null | Toxicity | null | Curation Efforts|Research and Development | 36150341 | 0 | null | null | 9606 | null | null | 6 | 1 | null | null | null |
1917314 | Literature-derived | Inhibition of colchicine binding to tubulin (unknown origin) at 2 to 16 uM by competitive binding assay | Title: Discovery of polymethoxyphenyl-pyridines bearing amino side chains as tubulin colchicine-binding site inhibitors._||_Abstract: Nineteen TH03 analogues were designed and synthesized as tubulin colchicine-binding site inhibitors with potent antiproliferative activities. Among these compounds, 3,5-dimethoxyphenylpyridines 8j bearing a 4-methoxybenzyl aniline side-chain displayed the best antiproliferative activities against glioma (U87MG and U251). In addition, the trimethoxyphenylpyridine 8o bearing a 4-methyl-N-methyl aniline side-chain showed the best antiproliferative activities against colon carcinoma and lung cancer with the lowest IC<sub>50</sub> value (0.09 µM < IC<sub>50</sub> < 0.86 µM). Compared with CA-4, Compounds 8j and 8o displayed lower cytotoxicities toward normal cells but higher antiproliferative activities against RKO (IC<sub>50</sub> = 0.15 µM and 0.09 µM respectively), NCI-H1299 (IC<sub>50</sub> = 0.73 µM and 0.14 µM respectively), and A549 cells (IC<sub>50</sub> = 0.86 µM and 0.37 µM respectively). Further investigations revealed that 8o shows higher tubulin polymerization inhibitory activity (IC<sub>50</sub> = 3.1 ± 0.5 µM) than colchicine (IC<sub>50</sub> = 8.6 ± 0.2 µM), and induced cell cycle arrest at the G2/M phase and cellular apoptosis through disrupting the microtubule network. | Journal: Bioorg Med Chem_||_Year: 2022_||_Volume: 73_||_First Page: 117007_||_Last Page: 117007_||_DOI: 10.1016/j.bmc.2022.117007_||_Target ChEMBL ID: CHEMBL2095182_||_ChEMBL Target Name: Tubulin_||_ChEMBL Target Type: PROTEIN COMPLEX GROUP - Target is a poorly defined protein complex, where subunit composition is unclear (e.g., GABA-A receptor)_||_Relationship Type: D - Direct protein target assigned_||_Confidence: Multiple direct protein targets may be assigned | 43 | ChEMBL | CHEMBL5216836 | 20230629 | 20230629 | 168298477 | 482089005 | 7277|7278|7280|7846|10376|10381|10382|10383|81027|84617|84790|112714|203068|347688|347733 | null | P04350|P07437|P0DPH7|P68363|P68366|P68371|Q13509|Q13885|Q3ZCM7|Q6PEY2|Q71U36|Q9BQE3|Q9BUF5|Q9BVA1|Q9H4B7 | Curation Efforts|Research and Development | 36150341 | 0 | 3.6.5.- | P04350|P07437|P0DPH7|P68363|P68366|P68371|Q13509|Q13885|Q3ZCM7|Q6PEY2|Q71U36|Q9BQE3|Q9BUF5|Q9BVA1|Q9H4B7 | 9606 | null | null | 1 | 1 | null | null | null |
1917315 | Literature-derived | Disruption of microtubule network in human A549 cells at 600 nM measured after 24 hrs by immunofluorescence staining assay | Title: Discovery of polymethoxyphenyl-pyridines bearing amino side chains as tubulin colchicine-binding site inhibitors._||_Abstract: Nineteen TH03 analogues were designed and synthesized as tubulin colchicine-binding site inhibitors with potent antiproliferative activities. Among these compounds, 3,5-dimethoxyphenylpyridines 8j bearing a 4-methoxybenzyl aniline side-chain displayed the best antiproliferative activities against glioma (U87MG and U251). In addition, the trimethoxyphenylpyridine 8o bearing a 4-methyl-N-methyl aniline side-chain showed the best antiproliferative activities against colon carcinoma and lung cancer with the lowest IC<sub>50</sub> value (0.09 µM < IC<sub>50</sub> < 0.86 µM). Compared with CA-4, Compounds 8j and 8o displayed lower cytotoxicities toward normal cells but higher antiproliferative activities against RKO (IC<sub>50</sub> = 0.15 µM and 0.09 µM respectively), NCI-H1299 (IC<sub>50</sub> = 0.73 µM and 0.14 µM respectively), and A549 cells (IC<sub>50</sub> = 0.86 µM and 0.37 µM respectively). Further investigations revealed that 8o shows higher tubulin polymerization inhibitory activity (IC<sub>50</sub> = 3.1 ± 0.5 µM) than colchicine (IC<sub>50</sub> = 8.6 ± 0.2 µM), and induced cell cycle arrest at the G2/M phase and cellular apoptosis through disrupting the microtubule network. | Journal: Bioorg Med Chem_||_Year: 2022_||_Volume: 73_||_First Page: 117007_||_Last Page: 117007_||_DOI: 10.1016/j.bmc.2022.117007_||_Target ChEMBL ID: CHEMBL2095182_||_ChEMBL Target Name: Tubulin_||_ChEMBL Target Type: PROTEIN COMPLEX GROUP - Target is a poorly defined protein complex, where subunit composition is unclear (e.g., GABA-A receptor)_||_Relationship Type: D - Direct protein target assigned_||_Confidence: Multiple direct protein targets may be assigned | 43 | ChEMBL | CHEMBL5216837 | 20230629 | 20230629 | 168298477 | 482089005 | 7277|7278|7280|7846|10376|10381|10382|10383|81027|84617|84790|112714|203068|347688|347733 | null | P04350|P07437|P0DPH7|P68363|P68366|P68371|Q13509|Q13885|Q3ZCM7|Q6PEY2|Q71U36|Q9BQE3|Q9BUF5|Q9BVA1|Q9H4B7 | Curation Efforts|Research and Development | 36150341 | 0 | 3.6.5.- | P04350|P07437|P0DPH7|P68363|P68366|P68371|Q13509|Q13885|Q3ZCM7|Q6PEY2|Q71U36|Q9BQE3|Q9BUF5|Q9BVA1|Q9H4B7 | 9606 | null | null | 1 | 1 | null | null | null |
1917316 | Literature-derived | Induction of cell cycle arrest in human A549 cells assessed as accumulation of cells at G0/G1 phase at 150 nM measured after 24 hrs by flow cytometry analysis (Rvb= 70.5%) | Title: Discovery of polymethoxyphenyl-pyridines bearing amino side chains as tubulin colchicine-binding site inhibitors._||_Abstract: Nineteen TH03 analogues were designed and synthesized as tubulin colchicine-binding site inhibitors with potent antiproliferative activities. Among these compounds, 3,5-dimethoxyphenylpyridines 8j bearing a 4-methoxybenzyl aniline side-chain displayed the best antiproliferative activities against glioma (U87MG and U251). In addition, the trimethoxyphenylpyridine 8o bearing a 4-methyl-N-methyl aniline side-chain showed the best antiproliferative activities against colon carcinoma and lung cancer with the lowest IC<sub>50</sub> value (0.09 µM < IC<sub>50</sub> < 0.86 µM). Compared with CA-4, Compounds 8j and 8o displayed lower cytotoxicities toward normal cells but higher antiproliferative activities against RKO (IC<sub>50</sub> = 0.15 µM and 0.09 µM respectively), NCI-H1299 (IC<sub>50</sub> = 0.73 µM and 0.14 µM respectively), and A549 cells (IC<sub>50</sub> = 0.86 µM and 0.37 µM respectively). Further investigations revealed that 8o shows higher tubulin polymerization inhibitory activity (IC<sub>50</sub> = 3.1 ± 0.5 µM) than colchicine (IC<sub>50</sub> = 8.6 ± 0.2 µM), and induced cell cycle arrest at the G2/M phase and cellular apoptosis through disrupting the microtubule network. | Journal: Bioorg Med Chem_||_Year: 2022_||_Volume: 73_||_First Page: 117007_||_Last Page: 117007_||_DOI: 10.1016/j.bmc.2022.117007_||_Target ChEMBL ID: CHEMBL392_||_ChEMBL Target Name: A549_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5216838 | 20230629 | 20230629 | 168298477 | 482089005 | null | null | null | Curation Efforts|Research and Development | 36150341 | 0 | null | null | 9606 | null | null | 1 | null | null | null | null |
1917317 | Literature-derived | Induction of cell cycle arrest in human A549 cells assessed as accumulation of cells at G2/M phase at 150 nM measured after 24 hrs by flow cytometry analysis (Rvb= 8.85%) | Title: Discovery of polymethoxyphenyl-pyridines bearing amino side chains as tubulin colchicine-binding site inhibitors._||_Abstract: Nineteen TH03 analogues were designed and synthesized as tubulin colchicine-binding site inhibitors with potent antiproliferative activities. Among these compounds, 3,5-dimethoxyphenylpyridines 8j bearing a 4-methoxybenzyl aniline side-chain displayed the best antiproliferative activities against glioma (U87MG and U251). In addition, the trimethoxyphenylpyridine 8o bearing a 4-methyl-N-methyl aniline side-chain showed the best antiproliferative activities against colon carcinoma and lung cancer with the lowest IC<sub>50</sub> value (0.09 µM < IC<sub>50</sub> < 0.86 µM). Compared with CA-4, Compounds 8j and 8o displayed lower cytotoxicities toward normal cells but higher antiproliferative activities against RKO (IC<sub>50</sub> = 0.15 µM and 0.09 µM respectively), NCI-H1299 (IC<sub>50</sub> = 0.73 µM and 0.14 µM respectively), and A549 cells (IC<sub>50</sub> = 0.86 µM and 0.37 µM respectively). Further investigations revealed that 8o shows higher tubulin polymerization inhibitory activity (IC<sub>50</sub> = 3.1 ± 0.5 µM) than colchicine (IC<sub>50</sub> = 8.6 ± 0.2 µM), and induced cell cycle arrest at the G2/M phase and cellular apoptosis through disrupting the microtubule network. | Journal: Bioorg Med Chem_||_Year: 2022_||_Volume: 73_||_First Page: 117007_||_Last Page: 117007_||_DOI: 10.1016/j.bmc.2022.117007_||_Target ChEMBL ID: CHEMBL392_||_ChEMBL Target Name: A549_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5216839 | 20230629 | 20230629 | 168298477 | 482089005 | null | null | null | Curation Efforts|Research and Development | 36150341 | 0 | null | null | 9606 | null | null | 1 | null | null | null | null |
1917318 | Literature-derived | Induction of cell cycle arrest in human A549 cells assessed as accumulation of cells at S phase at 150 nM measured after 24 hrs by flow cytometry analysis (Rvb= 20.65%) | Title: Discovery of polymethoxyphenyl-pyridines bearing amino side chains as tubulin colchicine-binding site inhibitors._||_Abstract: Nineteen TH03 analogues were designed and synthesized as tubulin colchicine-binding site inhibitors with potent antiproliferative activities. Among these compounds, 3,5-dimethoxyphenylpyridines 8j bearing a 4-methoxybenzyl aniline side-chain displayed the best antiproliferative activities against glioma (U87MG and U251). In addition, the trimethoxyphenylpyridine 8o bearing a 4-methyl-N-methyl aniline side-chain showed the best antiproliferative activities against colon carcinoma and lung cancer with the lowest IC<sub>50</sub> value (0.09 µM < IC<sub>50</sub> < 0.86 µM). Compared with CA-4, Compounds 8j and 8o displayed lower cytotoxicities toward normal cells but higher antiproliferative activities against RKO (IC<sub>50</sub> = 0.15 µM and 0.09 µM respectively), NCI-H1299 (IC<sub>50</sub> = 0.73 µM and 0.14 µM respectively), and A549 cells (IC<sub>50</sub> = 0.86 µM and 0.37 µM respectively). Further investigations revealed that 8o shows higher tubulin polymerization inhibitory activity (IC<sub>50</sub> = 3.1 ± 0.5 µM) than colchicine (IC<sub>50</sub> = 8.6 ± 0.2 µM), and induced cell cycle arrest at the G2/M phase and cellular apoptosis through disrupting the microtubule network. | Journal: Bioorg Med Chem_||_Year: 2022_||_Volume: 73_||_First Page: 117007_||_Last Page: 117007_||_DOI: 10.1016/j.bmc.2022.117007_||_Target ChEMBL ID: CHEMBL392_||_ChEMBL Target Name: A549_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5216840 | 20230629 | 20230629 | 168298477 | 482089005 | null | null | null | Curation Efforts|Research and Development | 36150341 | 0 | null | null | 9606 | null | null | 1 | null | null | null | null |
1917319 | Literature-derived | Induction of cell cycle arrest in human A549 cells assessed as accumulation of cells at G0/G1 phase at 300 nM measured after 24 hrs by flow cytometry analysis (Rvb= 70.5%) | Title: Discovery of polymethoxyphenyl-pyridines bearing amino side chains as tubulin colchicine-binding site inhibitors._||_Abstract: Nineteen TH03 analogues were designed and synthesized as tubulin colchicine-binding site inhibitors with potent antiproliferative activities. Among these compounds, 3,5-dimethoxyphenylpyridines 8j bearing a 4-methoxybenzyl aniline side-chain displayed the best antiproliferative activities against glioma (U87MG and U251). In addition, the trimethoxyphenylpyridine 8o bearing a 4-methyl-N-methyl aniline side-chain showed the best antiproliferative activities against colon carcinoma and lung cancer with the lowest IC<sub>50</sub> value (0.09 µM < IC<sub>50</sub> < 0.86 µM). Compared with CA-4, Compounds 8j and 8o displayed lower cytotoxicities toward normal cells but higher antiproliferative activities against RKO (IC<sub>50</sub> = 0.15 µM and 0.09 µM respectively), NCI-H1299 (IC<sub>50</sub> = 0.73 µM and 0.14 µM respectively), and A549 cells (IC<sub>50</sub> = 0.86 µM and 0.37 µM respectively). Further investigations revealed that 8o shows higher tubulin polymerization inhibitory activity (IC<sub>50</sub> = 3.1 ± 0.5 µM) than colchicine (IC<sub>50</sub> = 8.6 ± 0.2 µM), and induced cell cycle arrest at the G2/M phase and cellular apoptosis through disrupting the microtubule network. | Journal: Bioorg Med Chem_||_Year: 2022_||_Volume: 73_||_First Page: 117007_||_Last Page: 117007_||_DOI: 10.1016/j.bmc.2022.117007_||_Target ChEMBL ID: CHEMBL392_||_ChEMBL Target Name: A549_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5216841 | 20230629 | 20230629 | 168298477 | 482089005 | null | null | null | Curation Efforts|Research and Development | 36150341 | 0 | null | null | 9606 | null | null | 1 | null | null | null | null |
1917320 | Literature-derived | Induction of cell cycle arrest in human A549 cells assessed as accumulation of cells at G2/M phase at 300 nM measured after 24 hrs by flow cytometry analysis (Rvb= 8.85%) | Title: Discovery of polymethoxyphenyl-pyridines bearing amino side chains as tubulin colchicine-binding site inhibitors._||_Abstract: Nineteen TH03 analogues were designed and synthesized as tubulin colchicine-binding site inhibitors with potent antiproliferative activities. Among these compounds, 3,5-dimethoxyphenylpyridines 8j bearing a 4-methoxybenzyl aniline side-chain displayed the best antiproliferative activities against glioma (U87MG and U251). In addition, the trimethoxyphenylpyridine 8o bearing a 4-methyl-N-methyl aniline side-chain showed the best antiproliferative activities against colon carcinoma and lung cancer with the lowest IC<sub>50</sub> value (0.09 µM < IC<sub>50</sub> < 0.86 µM). Compared with CA-4, Compounds 8j and 8o displayed lower cytotoxicities toward normal cells but higher antiproliferative activities against RKO (IC<sub>50</sub> = 0.15 µM and 0.09 µM respectively), NCI-H1299 (IC<sub>50</sub> = 0.73 µM and 0.14 µM respectively), and A549 cells (IC<sub>50</sub> = 0.86 µM and 0.37 µM respectively). Further investigations revealed that 8o shows higher tubulin polymerization inhibitory activity (IC<sub>50</sub> = 3.1 ± 0.5 µM) than colchicine (IC<sub>50</sub> = 8.6 ± 0.2 µM), and induced cell cycle arrest at the G2/M phase and cellular apoptosis through disrupting the microtubule network. | Journal: Bioorg Med Chem_||_Year: 2022_||_Volume: 73_||_First Page: 117007_||_Last Page: 117007_||_DOI: 10.1016/j.bmc.2022.117007_||_Target ChEMBL ID: CHEMBL392_||_ChEMBL Target Name: A549_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5216842 | 20230629 | 20230629 | 168298477 | 482089005 | null | null | null | Curation Efforts|Research and Development | 36150341 | 0 | null | null | 9606 | null | null | 1 | null | null | null | null |
1917321 | Literature-derived | Induction of cell cycle arrest in human A549 cells assessed as accumulation of cells at S phase at 300 nM measured after 24 hrs by flow cytometry analysis (Rvb= 20.65%) | Title: Discovery of polymethoxyphenyl-pyridines bearing amino side chains as tubulin colchicine-binding site inhibitors._||_Abstract: Nineteen TH03 analogues were designed and synthesized as tubulin colchicine-binding site inhibitors with potent antiproliferative activities. Among these compounds, 3,5-dimethoxyphenylpyridines 8j bearing a 4-methoxybenzyl aniline side-chain displayed the best antiproliferative activities against glioma (U87MG and U251). In addition, the trimethoxyphenylpyridine 8o bearing a 4-methyl-N-methyl aniline side-chain showed the best antiproliferative activities against colon carcinoma and lung cancer with the lowest IC<sub>50</sub> value (0.09 µM < IC<sub>50</sub> < 0.86 µM). Compared with CA-4, Compounds 8j and 8o displayed lower cytotoxicities toward normal cells but higher antiproliferative activities against RKO (IC<sub>50</sub> = 0.15 µM and 0.09 µM respectively), NCI-H1299 (IC<sub>50</sub> = 0.73 µM and 0.14 µM respectively), and A549 cells (IC<sub>50</sub> = 0.86 µM and 0.37 µM respectively). Further investigations revealed that 8o shows higher tubulin polymerization inhibitory activity (IC<sub>50</sub> = 3.1 ± 0.5 µM) than colchicine (IC<sub>50</sub> = 8.6 ± 0.2 µM), and induced cell cycle arrest at the G2/M phase and cellular apoptosis through disrupting the microtubule network. | Journal: Bioorg Med Chem_||_Year: 2022_||_Volume: 73_||_First Page: 117007_||_Last Page: 117007_||_DOI: 10.1016/j.bmc.2022.117007_||_Target ChEMBL ID: CHEMBL392_||_ChEMBL Target Name: A549_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5216843 | 20230629 | 20230629 | 168298477 | 482089005 | null | null | null | Curation Efforts|Research and Development | 36150341 | 0 | null | null | 9606 | null | null | 1 | null | null | null | null |
1917322 | Literature-derived | Induction of cell cycle arrest in human A549 cells assessed as accumulation of cells at G0/G1 phase at 600 nM measured after 24 hrs by flow cytometry analysis (Rvb= 70.5%) | Title: Discovery of polymethoxyphenyl-pyridines bearing amino side chains as tubulin colchicine-binding site inhibitors._||_Abstract: Nineteen TH03 analogues were designed and synthesized as tubulin colchicine-binding site inhibitors with potent antiproliferative activities. Among these compounds, 3,5-dimethoxyphenylpyridines 8j bearing a 4-methoxybenzyl aniline side-chain displayed the best antiproliferative activities against glioma (U87MG and U251). In addition, the trimethoxyphenylpyridine 8o bearing a 4-methyl-N-methyl aniline side-chain showed the best antiproliferative activities against colon carcinoma and lung cancer with the lowest IC<sub>50</sub> value (0.09 µM < IC<sub>50</sub> < 0.86 µM). Compared with CA-4, Compounds 8j and 8o displayed lower cytotoxicities toward normal cells but higher antiproliferative activities against RKO (IC<sub>50</sub> = 0.15 µM and 0.09 µM respectively), NCI-H1299 (IC<sub>50</sub> = 0.73 µM and 0.14 µM respectively), and A549 cells (IC<sub>50</sub> = 0.86 µM and 0.37 µM respectively). Further investigations revealed that 8o shows higher tubulin polymerization inhibitory activity (IC<sub>50</sub> = 3.1 ± 0.5 µM) than colchicine (IC<sub>50</sub> = 8.6 ± 0.2 µM), and induced cell cycle arrest at the G2/M phase and cellular apoptosis through disrupting the microtubule network. | Journal: Bioorg Med Chem_||_Year: 2022_||_Volume: 73_||_First Page: 117007_||_Last Page: 117007_||_DOI: 10.1016/j.bmc.2022.117007_||_Target ChEMBL ID: CHEMBL392_||_ChEMBL Target Name: A549_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5216844 | 20230629 | 20230629 | 168298477 | 482089005 | null | null | null | Curation Efforts|Research and Development | 36150341 | 0 | null | null | 9606 | null | null | 1 | null | null | null | null |
1917323 | Literature-derived | Induction of cell cycle arrest in human A549 cells assessed as accumulation of cells at G2/M phase at 600 nM measured after 24 hrs by flow cytometry analysis (Rvb= 8.85%) | Title: Discovery of polymethoxyphenyl-pyridines bearing amino side chains as tubulin colchicine-binding site inhibitors._||_Abstract: Nineteen TH03 analogues were designed and synthesized as tubulin colchicine-binding site inhibitors with potent antiproliferative activities. Among these compounds, 3,5-dimethoxyphenylpyridines 8j bearing a 4-methoxybenzyl aniline side-chain displayed the best antiproliferative activities against glioma (U87MG and U251). In addition, the trimethoxyphenylpyridine 8o bearing a 4-methyl-N-methyl aniline side-chain showed the best antiproliferative activities against colon carcinoma and lung cancer with the lowest IC<sub>50</sub> value (0.09 µM < IC<sub>50</sub> < 0.86 µM). Compared with CA-4, Compounds 8j and 8o displayed lower cytotoxicities toward normal cells but higher antiproliferative activities against RKO (IC<sub>50</sub> = 0.15 µM and 0.09 µM respectively), NCI-H1299 (IC<sub>50</sub> = 0.73 µM and 0.14 µM respectively), and A549 cells (IC<sub>50</sub> = 0.86 µM and 0.37 µM respectively). Further investigations revealed that 8o shows higher tubulin polymerization inhibitory activity (IC<sub>50</sub> = 3.1 ± 0.5 µM) than colchicine (IC<sub>50</sub> = 8.6 ± 0.2 µM), and induced cell cycle arrest at the G2/M phase and cellular apoptosis through disrupting the microtubule network. | Journal: Bioorg Med Chem_||_Year: 2022_||_Volume: 73_||_First Page: 117007_||_Last Page: 117007_||_DOI: 10.1016/j.bmc.2022.117007_||_Target ChEMBL ID: CHEMBL392_||_ChEMBL Target Name: A549_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5216845 | 20230629 | 20230629 | 168298477 | 482089005 | null | null | null | Curation Efforts|Research and Development | 36150341 | 0 | null | null | 9606 | null | null | 1 | null | null | null | null |
1917324 | Literature-derived | Induction of cell cycle arrest in human A549 cells assessed as accumulation of cells at S phase at 600 nM measured after 24 hrs by flow cytometry analysis (Rvb= 20.65%) | Title: Discovery of polymethoxyphenyl-pyridines bearing amino side chains as tubulin colchicine-binding site inhibitors._||_Abstract: Nineteen TH03 analogues were designed and synthesized as tubulin colchicine-binding site inhibitors with potent antiproliferative activities. Among these compounds, 3,5-dimethoxyphenylpyridines 8j bearing a 4-methoxybenzyl aniline side-chain displayed the best antiproliferative activities against glioma (U87MG and U251). In addition, the trimethoxyphenylpyridine 8o bearing a 4-methyl-N-methyl aniline side-chain showed the best antiproliferative activities against colon carcinoma and lung cancer with the lowest IC<sub>50</sub> value (0.09 µM < IC<sub>50</sub> < 0.86 µM). Compared with CA-4, Compounds 8j and 8o displayed lower cytotoxicities toward normal cells but higher antiproliferative activities against RKO (IC<sub>50</sub> = 0.15 µM and 0.09 µM respectively), NCI-H1299 (IC<sub>50</sub> = 0.73 µM and 0.14 µM respectively), and A549 cells (IC<sub>50</sub> = 0.86 µM and 0.37 µM respectively). Further investigations revealed that 8o shows higher tubulin polymerization inhibitory activity (IC<sub>50</sub> = 3.1 ± 0.5 µM) than colchicine (IC<sub>50</sub> = 8.6 ± 0.2 µM), and induced cell cycle arrest at the G2/M phase and cellular apoptosis through disrupting the microtubule network. | Journal: Bioorg Med Chem_||_Year: 2022_||_Volume: 73_||_First Page: 117007_||_Last Page: 117007_||_DOI: 10.1016/j.bmc.2022.117007_||_Target ChEMBL ID: CHEMBL392_||_ChEMBL Target Name: A549_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5216846 | 20230629 | 20230629 | 168298477 | 482089005 | null | null | null | Curation Efforts|Research and Development | 36150341 | 0 | null | null | 9606 | null | null | 1 | null | null | null | null |
1917325 | Literature-derived | Induction of apoptosis in human A549 cells assessed as total apoptotic cells at 150 nM measured after 48 hrs by Annexin V-FITC/PI staining based flow cytometry analysis | Title: Discovery of polymethoxyphenyl-pyridines bearing amino side chains as tubulin colchicine-binding site inhibitors._||_Abstract: Nineteen TH03 analogues were designed and synthesized as tubulin colchicine-binding site inhibitors with potent antiproliferative activities. Among these compounds, 3,5-dimethoxyphenylpyridines 8j bearing a 4-methoxybenzyl aniline side-chain displayed the best antiproliferative activities against glioma (U87MG and U251). In addition, the trimethoxyphenylpyridine 8o bearing a 4-methyl-N-methyl aniline side-chain showed the best antiproliferative activities against colon carcinoma and lung cancer with the lowest IC<sub>50</sub> value (0.09 µM < IC<sub>50</sub> < 0.86 µM). Compared with CA-4, Compounds 8j and 8o displayed lower cytotoxicities toward normal cells but higher antiproliferative activities against RKO (IC<sub>50</sub> = 0.15 µM and 0.09 µM respectively), NCI-H1299 (IC<sub>50</sub> = 0.73 µM and 0.14 µM respectively), and A549 cells (IC<sub>50</sub> = 0.86 µM and 0.37 µM respectively). Further investigations revealed that 8o shows higher tubulin polymerization inhibitory activity (IC<sub>50</sub> = 3.1 ± 0.5 µM) than colchicine (IC<sub>50</sub> = 8.6 ± 0.2 µM), and induced cell cycle arrest at the G2/M phase and cellular apoptosis through disrupting the microtubule network. | Journal: Bioorg Med Chem_||_Year: 2022_||_Volume: 73_||_First Page: 117007_||_Last Page: 117007_||_DOI: 10.1016/j.bmc.2022.117007_||_Target ChEMBL ID: CHEMBL392_||_ChEMBL Target Name: A549_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5216847 | 20230629 | 20230629 | 168298477 | 482089005 | null | null | null | Curation Efforts|Research and Development | 36150341 | 0 | null | null | 9606 | null | null | 1 | null | null | null | null |
1917326 | Literature-derived | Induction of apoptosis in human A549 cells assessed as total apoptotic cells at 300 nM measured after 48 hrs by Annexin V-FITC/PI staining based flow cytometry analysis | Title: Discovery of polymethoxyphenyl-pyridines bearing amino side chains as tubulin colchicine-binding site inhibitors._||_Abstract: Nineteen TH03 analogues were designed and synthesized as tubulin colchicine-binding site inhibitors with potent antiproliferative activities. Among these compounds, 3,5-dimethoxyphenylpyridines 8j bearing a 4-methoxybenzyl aniline side-chain displayed the best antiproliferative activities against glioma (U87MG and U251). In addition, the trimethoxyphenylpyridine 8o bearing a 4-methyl-N-methyl aniline side-chain showed the best antiproliferative activities against colon carcinoma and lung cancer with the lowest IC<sub>50</sub> value (0.09 µM < IC<sub>50</sub> < 0.86 µM). Compared with CA-4, Compounds 8j and 8o displayed lower cytotoxicities toward normal cells but higher antiproliferative activities against RKO (IC<sub>50</sub> = 0.15 µM and 0.09 µM respectively), NCI-H1299 (IC<sub>50</sub> = 0.73 µM and 0.14 µM respectively), and A549 cells (IC<sub>50</sub> = 0.86 µM and 0.37 µM respectively). Further investigations revealed that 8o shows higher tubulin polymerization inhibitory activity (IC<sub>50</sub> = 3.1 ± 0.5 µM) than colchicine (IC<sub>50</sub> = 8.6 ± 0.2 µM), and induced cell cycle arrest at the G2/M phase and cellular apoptosis through disrupting the microtubule network. | Journal: Bioorg Med Chem_||_Year: 2022_||_Volume: 73_||_First Page: 117007_||_Last Page: 117007_||_DOI: 10.1016/j.bmc.2022.117007_||_Target ChEMBL ID: CHEMBL392_||_ChEMBL Target Name: A549_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5216848 | 20230629 | 20230629 | 168298477 | 482089005 | null | null | null | Curation Efforts|Research and Development | 36150341 | 0 | null | null | 9606 | null | null | 1 | null | null | null | null |
1917327 | Literature-derived | Induction of apoptosis in human A549 cells assessed as total apoptotic cells at 600 nM measured after 48 hrs by Annexin V-FITC/PI staining based flow cytometry analysis | Title: Discovery of polymethoxyphenyl-pyridines bearing amino side chains as tubulin colchicine-binding site inhibitors._||_Abstract: Nineteen TH03 analogues were designed and synthesized as tubulin colchicine-binding site inhibitors with potent antiproliferative activities. Among these compounds, 3,5-dimethoxyphenylpyridines 8j bearing a 4-methoxybenzyl aniline side-chain displayed the best antiproliferative activities against glioma (U87MG and U251). In addition, the trimethoxyphenylpyridine 8o bearing a 4-methyl-N-methyl aniline side-chain showed the best antiproliferative activities against colon carcinoma and lung cancer with the lowest IC<sub>50</sub> value (0.09 µM < IC<sub>50</sub> < 0.86 µM). Compared with CA-4, Compounds 8j and 8o displayed lower cytotoxicities toward normal cells but higher antiproliferative activities against RKO (IC<sub>50</sub> = 0.15 µM and 0.09 µM respectively), NCI-H1299 (IC<sub>50</sub> = 0.73 µM and 0.14 µM respectively), and A549 cells (IC<sub>50</sub> = 0.86 µM and 0.37 µM respectively). Further investigations revealed that 8o shows higher tubulin polymerization inhibitory activity (IC<sub>50</sub> = 3.1 ± 0.5 µM) than colchicine (IC<sub>50</sub> = 8.6 ± 0.2 µM), and induced cell cycle arrest at the G2/M phase and cellular apoptosis through disrupting the microtubule network. | Journal: Bioorg Med Chem_||_Year: 2022_||_Volume: 73_||_First Page: 117007_||_Last Page: 117007_||_DOI: 10.1016/j.bmc.2022.117007_||_Target ChEMBL ID: CHEMBL392_||_ChEMBL Target Name: A549_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5216849 | 20230629 | 20230629 | 168298477 | 482089005 | null | null | null | Curation Efforts|Research and Development | 36150341 | 0 | null | null | 9606 | null | null | 1 | null | null | null | null |
1918006 | Confirmatory | Anticancer activity against human A498 cells assessed as cell growth inhibition | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Compounds with activity <= 10uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation._||_Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431_||_Target ChEMBL ID: CHEMBL614516_||_ChEMBL Target Name: A498_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5217528 | 20230629 | 20230629 | 16739305|24861508 | 103530118|482089946 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 9606 | null | null | 2 | 2 | null | null | null |
1918007 | Confirmatory | Anticancer activity against human Panel NCI-60 (60 carcinoma cell lines) cells assessed as cell growth inhibition | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Compounds with activity <= 10uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation._||_Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431_||_Target ChEMBL ID: CHEMBL614194_||_ChEMBL Target Name: Panel NCI-60 (60 carcinoma cell lines)_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5217529 | 20230629 | 20230629 | 16739305 | 103530118 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 9606 | null | null | 1 | 1 | null | null | null |
1918008 | Confirmatory | Anticancer activity against human MCF7 cells assessed as cell growth inhibition | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Compounds with activity <= 10uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation._||_Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431_||_Target ChEMBL ID: CHEMBL387_||_ChEMBL Target Name: MCF7_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5217530 | 20230629 | 20230629 | 11952815 | 103488700 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 9606 | null | null | 1 | 1 | null | null | null |
1918009 | Confirmatory | Anticancer activity against human MDA-MB-231 cells assessed as cell growth inhibition | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431_||_Target ChEMBL ID: CHEMBL400_||_ChEMBL Target Name: MDA-MB-231_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5217531 | 20230629 | 20230629 | 11952815 | 103488700 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 9606 | null | null | 1 | null | null | null | null |
1918010 | Confirmatory | Anticancer activity against human NCI-H661 cells assessed as cell growth inhibition | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Compounds with activity <= 10uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation._||_Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431_||_Target ChEMBL ID: CHEMBL1075544_||_ChEMBL Target Name: NCI-H661_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5217532 | 20230629 | 20230629 | 23625920 | 103536997 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 9606 | null | null | 1 | 1 | null | null | null |
1918011 | Confirmatory | Antagonist activity at GCNF (unknown origin) by luciferase reporter gene assay | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Compounds with activity <= 10uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation._||_Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431_||_Target ChEMBL ID: CHEMBL1961793_||_ChEMBL Target Name: Nuclear receptor subfamily 6 group A member 1_||_ChEMBL Target Type: SINGLE PROTEIN - Target is a single protein chain_||_Relationship Type: D - Direct protein target assigned_||_Confidence: Direct single protein target assigned | 43 | ChEMBL | CHEMBL5217533 | 20230629 | 20230629 | 24861508 | 482089946 | 2649 | null | Q15406 | Curation Efforts|Research and Development | 36260776 | 0 | null | Q15406 | 9606 | null | null | 1 | 1 | null | null | null |
1918012 | Confirmatory | Anticancer activity against human A549 cells assessed as cell growth inhibition measured after 48 hrs by SRB assay | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Compounds with activity <= 10uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation._||_Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431_||_Target ChEMBL ID: CHEMBL392_||_ChEMBL Target Name: A549_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5217534 | 20230629 | 20230629 | 168298185|168298189|168298220|168298226|168298252|168298402|168298411|168298427|168298433|168298551|168298578|168298607|168298609|168298649|168298682|168298686|168298701|168298713|168298802|168298803|168298837|168298867|168298868|168298879|168298883|168298997|168299133|168299159|168299251|168299278|168299282|168299316|168299334|168299348|168299402|168299445|168299451|168299474|168299491|168299518|168299523|168299578|168299588|168299597|168299676|168299692|168299714|168299726|168299747|168299798|168299806 | 482088606|482088613|482088660|482088667|482088702|482088908|482088918|482088939|482088947|482089106|482089142|482089181|482089183|482089236|482089280|482089284|482089308|482089326|482089452|482089453|482089499|482089543|482089544|482089559|482089566|482089722|482089906|482089944|482090075|482090112|482090117|482090168|482090192|482090215|482090284|482090341|482090349|482090378|482090400|482090435|482090443|482090523|482090536|482090546|482090667|482090691|482090717|482090731|482090759|482090835|482090847 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 9606 | null | null | 51 | 31 | null | null | null |
1918013 | Confirmatory | Anticancer activity against human HCT-116 cells assessed as cell growth inhibition measured after 48 hrs by SRB assay | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Compounds with activity <= 10uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation._||_Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431_||_Target ChEMBL ID: CHEMBL394_||_ChEMBL Target Name: HCT-116_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5217535 | 20230629 | 20230629 | 168298185|168298189|168298220|168298226|168298252|168298402|168298411|168298427|168298433|168298551|168298578|168298607|168298609|168298649|168298682|168298686|168298701|168298713|168298802|168298803|168298837|168298867|168298868|168298879|168298883|168298997|168299133|168299159|168299251|168299278|168299282|168299316|168299334|168299348|168299402|168299445|168299451|168299474|168299491|168299518|168299523|168299578|168299588|168299597|168299676|168299692|168299714|168299726|168299747|168299798|168299806 | 482088606|482088613|482088660|482088667|482088702|482088908|482088918|482088939|482088947|482089106|482089142|482089181|482089183|482089236|482089280|482089284|482089308|482089326|482089452|482089453|482089499|482089543|482089544|482089559|482089566|482089722|482089906|482089944|482090075|482090112|482090117|482090168|482090192|482090215|482090284|482090341|482090349|482090378|482090400|482090435|482090443|482090523|482090536|482090546|482090667|482090691|482090717|482090731|482090759|482090835|482090847 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 9606 | null | null | 51 | 30 | null | null | null |
1918014 | Confirmatory | Anticancer activity against human SF-295 cells assessed as cell growth inhibition measured after 48 hrs by SRB assay | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Compounds with activity <= 10uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation._||_Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431_||_Target ChEMBL ID: CHEMBL614908_||_ChEMBL Target Name: SF-295_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5217536 | 20230629 | 20230629 | 168298185|168298189|168298220|168298226|168298252|168298402|168298411|168298427|168298433|168298551|168298578|168298607|168298609|168298649|168298682|168298686|168298701|168298713|168298802|168298803|168298837|168298867|168298868|168298879|168298883|168298997|168299133|168299159|168299251|168299278|168299282|168299316|168299334|168299348|168299402|168299445|168299451|168299474|168299491|168299518|168299523|168299578|168299588|168299597|168299676|168299692|168299714|168299726|168299747|168299798|168299806 | 482088606|482088613|482088660|482088667|482088702|482088908|482088918|482088939|482088947|482089106|482089142|482089181|482089183|482089236|482089280|482089284|482089308|482089326|482089452|482089453|482089499|482089543|482089544|482089559|482089566|482089722|482089906|482089944|482090075|482090112|482090117|482090168|482090192|482090215|482090284|482090341|482090349|482090378|482090400|482090435|482090443|482090523|482090536|482090546|482090667|482090691|482090717|482090731|482090759|482090835|482090847 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 9606 | null | null | 51 | 30 | null | null | null |
1918015 | Confirmatory | Anticancer activity against human LOX IMVI cells assessed as cell growth inhibition measured after 48 hrs by SRB assay | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Compounds with activity <= 10uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation._||_Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431_||_Target ChEMBL ID: CHEMBL614096_||_ChEMBL Target Name: LOX IMVI_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5217537 | 20230629 | 20230629 | 168298185|168298189|168298220|168298226|168298252|168298402|168298411|168298427|168298433|168298551|168298578|168298607|168298609|168298649|168298682|168298686|168298701|168298713|168298802|168298803|168298837|168298867|168298868|168298879|168298883|168298997|168299133|168299159|168299251|168299278|168299282|168299316|168299334|168299348|168299402|168299445|168299451|168299474|168299491|168299518|168299523|168299578|168299588|168299597|168299676|168299692|168299714|168299726|168299747|168299798|168299806 | 482088606|482088613|482088660|482088667|482088702|482088908|482088918|482088939|482088947|482089106|482089142|482089181|482089183|482089236|482089280|482089284|482089308|482089326|482089452|482089453|482089499|482089543|482089544|482089559|482089566|482089722|482089906|482089944|482090075|482090112|482090117|482090168|482090192|482090215|482090284|482090341|482090349|482090378|482090400|482090435|482090443|482090523|482090536|482090546|482090667|482090691|482090717|482090731|482090759|482090835|482090847 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 9606 | null | null | 51 | 31 | null | null | null |
1918016 | Confirmatory | Anticancer activity against human 786-0 cells assessed as cell growth inhibition measured after 48 hrs by SRB assay | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Compounds with activity <= 10uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation._||_Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431_||_Target ChEMBL ID: CHEMBL613102_||_ChEMBL Target Name: 786-0_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5217538 | 20230629 | 20230629 | 168298185|168298189|168298220|168298226|168298252|168298402|168298411|168298427|168298433|168298551|168298578|168298607|168298609|168298649|168298682|168298686|168298701|168298802|168298803|168298837|168298867|168298868|168298879|168298883|168298997|168299133|168299159|168299251|168299278|168299282|168299316|168299334|168299348|168299402|168299445|168299451|168299474|168299491|168299518|168299523|168299578|168299588|168299597|168299676|168299692|168299714|168299726|168299747|168299798|168299806 | 482088606|482088613|482088660|482088667|482088702|482088908|482088918|482088939|482088947|482089106|482089142|482089181|482089183|482089236|482089280|482089284|482089308|482089452|482089453|482089499|482089543|482089544|482089559|482089566|482089722|482089906|482089944|482090075|482090112|482090117|482090168|482090192|482090215|482090284|482090341|482090349|482090378|482090400|482090435|482090443|482090523|482090536|482090546|482090667|482090691|482090717|482090731|482090759|482090835|482090847 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 9606 | null | null | 50 | 28 | null | null | null |
1918017 | Confirmatory | Anticancer activity against human Panel NCI-60 (60 carcinoma cell lines) line assessed as cell growth inhibition measured after 48 hrs by SRB assay | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Compounds with activity <= 10uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation._||_Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431_||_Target ChEMBL ID: CHEMBL614194_||_ChEMBL Target Name: Panel NCI-60 (60 carcinoma cell lines)_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5217539 | 20230629 | 20230629 | 168298185|168298189|168298220|168298226|168298252|168298402|168298411|168298427|168298433|168298551|168298578|168298607|168298609|168298649|168298682|168298686|168298701|168298713|168298802|168298803|168298837|168298867|168298868|168298879|168298997|168299133|168299159|168299251|168299278|168299282|168299316|168299402|168299445|168299451|168299474|168299491|168299518|168299523|168299578|168299588|168299597|168299676|168299692|168299714|168299726|168299747|168299798|168299806 | 482088606|482088613|482088660|482088667|482088702|482088908|482088918|482088939|482088947|482089106|482089142|482089181|482089183|482089236|482089280|482089284|482089308|482089326|482089452|482089453|482089499|482089543|482089544|482089559|482089722|482089906|482089944|482090075|482090112|482090117|482090168|482090284|482090341|482090349|482090378|482090400|482090435|482090443|482090523|482090536|482090546|482090667|482090691|482090717|482090731|482090759|482090835|482090847 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 9606 | null | null | 48 | 28 | null | null | null |
1918018 | Confirmatory | Inhibition of tubulin polymerization in mouse bone marrow-derived macrophages assessed as microtubule assembly measured every 1 min for 60 mins by fluorimeter analysis | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431 | 43 | ChEMBL | CHEMBL5217540 | 20230629 | 20230629 | 168298837 | 482089499 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 10090 | null | null | 1 | null | null | null | null |
1918019 | Literature-derived | Inhibition of hERG measured upto 50 uM | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431_||_Target ChEMBL ID: CHEMBL240_||_ChEMBL Target Name: HERG_||_ChEMBL Target Type: SINGLE PROTEIN - Target is a single protein chain_||_Relationship Type: D - Direct protein target assigned_||_Confidence: Direct single protein target assigned | 43 | ChEMBL | CHEMBL5217541 | 20230629 | 20230629 | 168298837 | 482089499 | 3757 | null | Q12809 | Curation Efforts|Research and Development | 36260776 | 0 | null | Q12809 | 9606 | null | null | 1 | null | null | null | null |
1918020 | Literature-derived | Induction of cell cycle arrest in human NCI-H460 cells assessed as accumulation at S phase at 20 nM incubated for 48 hrs by PI staining based flow cytometric analysis | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431_||_Target ChEMBL ID: CHEMBL396_||_ChEMBL Target Name: NCI-H460_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5217542 | 20230629 | 20230629 | 168298837 | 482089499 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 9606 | null | null | 1 | 1 | null | null | null |
1918021 | Literature-derived | Induction of cell cycle arrest in human NCI-H460 cells assessed as decrease in cyclin-A1 expression at 20 nM incubated for 24 hrs by Western blot analysis | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431_||_Target ChEMBL ID: CHEMBL396_||_ChEMBL Target Name: NCI-H460_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5217543 | 20230629 | 20230629 | 168298837|168299747 | 482089499|482090759 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 9606 | null | null | 2 | null | null | null | null |
1918022 | Literature-derived | Induction of cell cycle arrest in human NCI-H460 cells assessed as decrease in cyclin-D1 expression at 20 nM incubated for 24 hrs by Western blot analysis | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431_||_Target ChEMBL ID: CHEMBL396_||_ChEMBL Target Name: NCI-H460_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5217544 | 20230629 | 20230629 | 168298837|168299747 | 482089499|482090759 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 9606 | null | null | 2 | null | null | null | null |
1918023 | Literature-derived | Induction of cell cycle arrest in human NCI-H460 cells assessed as decrease in cyclin-E1 expression at 20 nM incubated for 24 hrs by Western blot analysis | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431_||_Target ChEMBL ID: CHEMBL396_||_ChEMBL Target Name: NCI-H460_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5217545 | 20230629 | 20230629 | 168298837|168299747 | 482089499|482090759 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 9606 | null | null | 2 | null | null | null | null |
1918024 | Literature-derived | Induction of apoptosis in human NCI-H522 cells assessed as viable cells at 0.05 uM incubated for 48 hrs by Annexin V-FITC/PI staining based flow cytometric analysis (Rvb = 82.4%) | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431_||_Target ChEMBL ID: CHEMBL614387_||_ChEMBL Target Name: NCI-H522_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5217546 | 20230629 | 20230629 | 168298837 | 482089499 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 9606 | null | null | 1 | null | null | null | null |
1918025 | Literature-derived | Induction of apoptosis in human NCI-H522 cells assessed as early apoptotic cells at 0.05 uM incubated for 48 hrs by Annexin V-FITC/PI staining based flow cytometric analysis (Rvb =7.01 %) | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431_||_Target ChEMBL ID: CHEMBL614387_||_ChEMBL Target Name: NCI-H522_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5217547 | 20230629 | 20230629 | 168298837 | 482089499 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 9606 | null | null | 1 | null | null | null | null |
1918026 | Literature-derived | Induction of apoptosis in human NCI-H522 cells assessed as late apoptotic cells at 0.05 uM incubated for 48 hrs by Annexin V-FITC/PI staining based flow cytometric analysis (Rvb =9.14 %) | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431_||_Target ChEMBL ID: CHEMBL614387_||_ChEMBL Target Name: NCI-H522_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5217548 | 20230629 | 20230629 | 168298837 | 482089499 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 9606 | null | null | 1 | null | null | null | null |
1918027 | Literature-derived | Induction of apoptosis in human NCI-H522 cells assessed as necrotic cells at 0.05 uM incubated for 48 hrs by Annexin V-FITC/PI staining based flow cytometric analysis (Rvb =0.64 %) | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431_||_Target ChEMBL ID: CHEMBL614387_||_ChEMBL Target Name: NCI-H522_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5217549 | 20230629 | 20230629 | 168298837 | 482089499 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 9606 | null | null | 1 | null | null | null | null |
1918028 | Literature-derived | Induction of apoptosis in human NCI-H522 cells assessed as viable cells at 0.5 uM incubated for 48 hrs by Annexin V-FITC/PI staining based flow cytometric analysis (Rvb = 82.4%) | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431_||_Target ChEMBL ID: CHEMBL614387_||_ChEMBL Target Name: NCI-H522_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5217550 | 20230629 | 20230629 | 168298837 | 482089499 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 9606 | null | null | 1 | null | null | null | null |
1918029 | Literature-derived | Induction of apoptosis in human NCI-H522 cells assessed as early apoptotic cells at 0.5 uM incubated for 48 hrs by Annexin V-FITC/PI staining based flow cytometric analysis (Rvb =7.01 %) | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431_||_Target ChEMBL ID: CHEMBL614387_||_ChEMBL Target Name: NCI-H522_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5217551 | 20230629 | 20230629 | 168298837 | 482089499 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 9606 | null | null | 1 | null | null | null | null |
1918030 | Literature-derived | Induction of apoptosis in human NCI-H522 cells assessed as late apoptotic cells at 0.5 uM incubated for 48 hrs by Annexin V-FITC/PI staining based flow cytometric analysis (Rvb =9.14 %) | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431_||_Target ChEMBL ID: CHEMBL614387_||_ChEMBL Target Name: NCI-H522_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5217552 | 20230629 | 20230629 | 168298837 | 482089499 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 9606 | null | null | 1 | null | null | null | null |
1918031 | Literature-derived | Induction of apoptosis in human NCI-H522 cells assessed as necrotic cells at 0.5 uM incubated for 48 hrs by Annexin V-FITC/PI staining based flow cytometric analysis (Rvb =0.64 %) | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431_||_Target ChEMBL ID: CHEMBL614387_||_ChEMBL Target Name: NCI-H522_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5217553 | 20230629 | 20230629 | 168298837 | 482089499 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 9606 | null | null | 1 | null | null | null | null |
1918032 | Literature-derived | Induction of apoptosis in human NCI-H522 cells assessed as viable cells at 5 uM incubated for 48 hrs by Annexin V-FITC/PI staining based flow cytometric analysis (Rvb = 82.4%) | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431_||_Target ChEMBL ID: CHEMBL614387_||_ChEMBL Target Name: NCI-H522_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5217554 | 20230629 | 20230629 | 168298837 | 482089499 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 9606 | null | null | 1 | null | null | null | null |
1918033 | Literature-derived | Induction of apoptosis in human NCI-H522 cells assessed as early apoptotic cells at 5 uM incubated for 48 hrs by Annexin V-FITC/PI staining based flow cytometric analysis (Rvb =7.01 %) | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431_||_Target ChEMBL ID: CHEMBL614387_||_ChEMBL Target Name: NCI-H522_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5217555 | 20230629 | 20230629 | 168298837 | 482089499 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 9606 | null | null | 1 | null | null | null | null |
1918034 | Literature-derived | Induction of apoptosis in human NCI-H522 cells assessed as late apoptotic cells at 5 uM incubated for 48 hrs by Annexin V-FITC/PI staining based flow cytometric analysis (Rvb =9.14 %) | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431_||_Target ChEMBL ID: CHEMBL614387_||_ChEMBL Target Name: NCI-H522_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5217556 | 20230629 | 20230629 | 168298837 | 482089499 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 9606 | null | null | 1 | null | null | null | null |
1918035 | Literature-derived | Induction of apoptosis in human NCI-H522 cells assessed as necrotic cells at 5 uM incubated for 48 hrs by Annexin V-FITC/PI staining based flow cytometric analysis (Rvb =0.64 %) | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431_||_Target ChEMBL ID: CHEMBL614387_||_ChEMBL Target Name: NCI-H522_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5217557 | 20230629 | 20230629 | 168298837 | 482089499 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 9606 | null | null | 1 | null | null | null | null |
1918036 | Literature-derived | Induction of apoptosis in human NCI-H522 cells assessed as apoptotic rate at 0.05 to 5 uM incubated for 48 hrs by AnnexinV-FITC/PI staining based flow cytometric analysis | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431_||_Target ChEMBL ID: CHEMBL614387_||_ChEMBL Target Name: NCI-H522_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5217558 | 20230629 | 20230629 | 168298837 | 482089499 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 9606 | null | null | 1 | null | null | null | null |
1918037 | Literature-derived | Induction of apoptosis in human NCI-H460 cells assessed as effect on cleavage of PARP at 1 uM measured for 48 hrs by western blot analysis | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431_||_Target ChEMBL ID: CHEMBL396_||_ChEMBL Target Name: NCI-H460_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5217559 | 20230629 | 20230629 | 168298837 | 482089499 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 9606 | null | null | 1 | 1 | null | null | null |
1918038 | Literature-derived | Induction of apoptosis in human NCI-H460 cells assessed as effect on caspase 3 level at 1 uM measured for 48 hrs by western blot analysis | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431_||_Target ChEMBL ID: CHEMBL396_||_ChEMBL Target Name: NCI-H460_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5217560 | 20230629 | 20230629 | 168298837 | 482089499 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 9606 | null | null | 1 | 1 | null | null | null |
1918039 | Literature-derived | Induction of apoptosis in human NCI-H460 cells assessed as effect on caspase 7 level at 1 uM measured for 48 hrs by western blot analysis | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431_||_Target ChEMBL ID: CHEMBL396_||_ChEMBL Target Name: NCI-H460_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5217561 | 20230629 | 20230629 | 168298837 | 482089499 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 9606 | null | null | 1 | 1 | null | null | null |
1918040 | Literature-derived | Induction of apoptosis in human NCI-H460 cells assessed as effect on caspase 9 level at 1 uM measured for 48 hrs by western blot analysis | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431_||_Target ChEMBL ID: CHEMBL396_||_ChEMBL Target Name: NCI-H460_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5217562 | 20230629 | 20230629 | 168298837 | 482089499 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 9606 | null | null | 1 | 1 | null | null | null |
1918041 | Literature-derived | Induction of mitochondrial membrane potential depolarization in human NCI-H522 cells measured after 48 hrs by JC-1 staining based flow cytometry analysis | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431_||_Target ChEMBL ID: CHEMBL614387_||_ChEMBL Target Name: NCI-H522_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5217563 | 20230629 | 20230629 | 168298837 | 482089499 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 9606 | null | null | 1 | null | null | null | null |
1918042 | Literature-derived | Downregulation of c-Myc protein expression level in human NCI-H460 cells at 20 nM incubated for 0.5 to 6 hrs by western blot analysis | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431 | 43 | ChEMBL | CHEMBL5217564 | 20230629 | 20230629 | 168298837 | 482089499 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 9606 | null | null | 1 | 1 | null | null | null |
1918043 | Literature-derived | Inhibition of polyribosome in human NCI-H460 cells assessed as decrease in 40S ribosome at 200 nM incubated for 1 hr in presence of cycloheximide | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431 | 43 | ChEMBL | CHEMBL5217565 | 20230629 | 20230629 | 168298837 | 482089499 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 9606 | null | null | 1 | null | null | null | null |
1918044 | Literature-derived | Inhibition of polyribosome in human NCI-H460 cells assessed as decrease in 60S ribosome at 200 nM incubated for 1 hr in presence of cycloheximide | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431 | 43 | ChEMBL | CHEMBL5217566 | 20230629 | 20230629 | 168298837 | 482089499 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 9606 | null | null | 1 | null | null | null | null |
1918045 | Literature-derived | Inhibition of polyribosome in human NCI-H460 cells assessed as increase in 80S ribosome at 200 nM incubated for 1 hr in presence of cycloheximide | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431 | 43 | ChEMBL | CHEMBL5217567 | 20230629 | 20230629 | 168298837 | 482089499 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 9606 | null | null | 1 | 1 | null | null | null |
1918046 | Confirmatory | Cmax in BALB/c nude mouse at 1 mg/kg, iv by LC-MS/MS analysis | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Compounds with activity <= 10uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation._||_Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431 | 43 | ChEMBL | CHEMBL5217568 | 20230629 | 20230629 | 168298837 | 482089499 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 10090 | null | null | 1 | 1 | null | null | null |
1918047 | Confirmatory | Cmax in BALB/c nude mouse at 10 mg/kg, po by LC-MS/MS analysis | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Compounds with activity <= 10uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation._||_Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431 | 43 | ChEMBL | CHEMBL5217569 | 20230629 | 20230629 | 168298837 | 482089499 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 10090 | null | null | 1 | 1 | null | null | null |
1918048 | Literature-derived | AUC (0 to t) in BALB/c nude mouse at 1 mg/kg, iv by LC-MS/MS analysis | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431 | 43 | ChEMBL | CHEMBL5217570 | 20230629 | 20230629 | 168298837 | 482089499 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 10090 | null | null | 1 | null | null | null | null |
1918049 | Literature-derived | AUC (0 to t) in BALB/c nude mouse at 10 mg/kg, po by LC-MS/MS analysis | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431 | 43 | ChEMBL | CHEMBL5217571 | 20230629 | 20230629 | 168298837 | 482089499 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 10090 | null | null | 1 | null | null | null | null |
1918050 | Literature-derived | Clearance in BALB/c nude mouse at 1 mg/kg, iv by LC-MS/MS analysis | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431 | 43 | ChEMBL | CHEMBL5217572 | 20230629 | 20230629 | 168298837 | 482089499 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 10090 | null | null | 1 | null | null | null | null |
1918051 | Literature-derived | Volume of distribution in steady state in BALB/c nude mouse at 1 mg/kg, iv by LC-MS/MS analysis | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431 | 43 | ChEMBL | CHEMBL5217573 | 20230629 | 20230629 | 168298837 | 482089499 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 10090 | null | null | 1 | null | null | null | null |
1918052 | Literature-derived | Half life in BALB/c nude mouse at 1 mg/kg, iv by LC-MS/MS analysis | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431 | 43 | ChEMBL | CHEMBL5217574 | 20230629 | 20230629 | 168298837 | 482089499 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 10090 | null | null | 1 | null | null | null | null |
1918053 | Literature-derived | Half life in BALB/c nude mouse at 10 mg/kg, po by LC-MS/MS analysis | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431 | 43 | ChEMBL | CHEMBL5217575 | 20230629 | 20230629 | 168298837 | 482089499 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 10090 | null | null | 1 | null | null | null | null |
1918054 | Literature-derived | Oral bioavailability in BALB/c nude mouse at 10 mg/kg by LC-MS/MS analysis | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431 | 43 | ChEMBL | CHEMBL5217576 | 20230629 | 20230629 | 168298837 | 482089499 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 10090 | null | null | 1 | null | null | null | null |
1918055 | Literature-derived | Antitumor activity against human NCI-H522 cells xenografted in iv dosed BALB/c nude mouse assessed as inhibition of tumor growth administered every 4 days for 21 days | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431_||_Target ChEMBL ID: CHEMBL614387_||_ChEMBL Target Name: NCI-H522_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5217577 | 20230629 | 20230629 | 168298837 | 482089499 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 9606 | null | null | 1 | null | null | null | null |
1918056 | Literature-derived | Antitumor activity against human NCI-H522 cells xenografted in BALB/c nude mouse assessed as reduction of tumor weight at 50 mg/kg, iv administered every 4 days for 21 days | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431_||_Target ChEMBL ID: CHEMBL614387_||_ChEMBL Target Name: NCI-H522_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5217578 | 20230629 | 20230629 | 168298837 | 482089499 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 9606 | null | null | 1 | null | null | null | null |
1918057 | Literature-derived | Antitumor activity against human NCI-H522 cells xenografted in BALB/c nude mouse assessed as reduction of tumor growth by measuring T/C ratio at 50 mg/kg, iv administered every 4 days for 21 days | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431_||_Target ChEMBL ID: CHEMBL614387_||_ChEMBL Target Name: NCI-H522_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5217579 | 20230629 | 20230629 | 168298837 | 482089499 | null | null | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 9606 | null | null | 1 | null | null | null | null |
1918058 | Literature-derived | Toxicity in BALB/c nude mouse xenografted with human NCI-H522 cells assessed as change in body weight at 12.5 to 50 mg/kg, iv administered every 4 days for 21 days | Title: Identification of 1,4-Benzodiazepine-2,5-dione Derivatives as Potential Protein Synthesis Inhibitors with Highly Potent Anticancer Activity._||_Abstract: In this study, a random multiple human tumor cell line screening of an in-stock small-molecule chemical library was performed, and a hit compound, 1,4-benzodiazepine-2,5-dione (BZD, <b>11a</b>; average 50% growth inhibitory concentration (GI<sub>50</sub> = 0.24 μM)) to 60 tumor cell lines of nine types of human cancers, was identified. Subsequent structure-activity relationship (SAR) investigation disclosed a highly potent antitumor compound, <b>52b</b>, that was shown to exert promising effects against lung cancer cells by inducing cell cycle arrest and apoptosis. Further polysome profile analysis revealed that <b>52b</b> inhibited protein synthesis in cancer cells. Moreover, <b>52b</b> significantly prevented tumor growth in a human non-small-cell lung cancer (NCI-H522) xenograft mouse model with no observable toxic effects. These findings are the first report of the synthetic compound <b>52b</b> with a 1,4-benzodiazepine-2,5-dione skeleton that acts as a potential protein synthesis inhibitor to effectively inhibit tumor growth. | Journal: J Med Chem_||_Year: 2022_||_Volume: 65_||_Issue: 21.0_||_First Page: 14891_||_Last Page: 14915_||_DOI: 10.1021/acs.jmedchem.2c01431 | 43 | ChEMBL | CHEMBL5217580 | 20230629 | 20230629 | 168298837 | 482089499 | null | Toxicity | null | Curation Efforts|Research and Development | 36260776 | 0 | null | null | 10090 | null | null | 1 | null | null | null | null |
1918195 | Confirmatory | Anticancer activity against human HepG2 cells assessed as inhibition of cell viability incubated for 72 hrs by MTT assay | Title: meta-Ureidophenoxy-1,2,3-triazole hybrid as a novel scaffold for promising HepG2 hepatocellular carcinoma inhibitors: Synthesis, biological evaluation and molecular docking studies._||_Abstract: Thirty-one meta-ureidophenoxymethyl-1,2,3-triazole derivatives were designed and synthesized via nucleophilic addition, nucleophilic substitution and copper-catalyzed azide-alkyne cycloaddition (CuAAC). The evaluation of their cytotoxicity using MTT assay indicated that almost all derivatives exhibited significantly superior inhibitory activity against hepatocellular carcinoma cell line HepG2 compared to the parental molecule sorafenib (1). Among the series, 5r was the most potent anti-HepG2 agent with IC<sub>50</sub> = 1.04 µM, which was almost 5-fold more active than sorafenib (IC<sub>50</sub> = 5.06 µM), while the cytotoxic activity against human embryonal lung fibroblast cell line MRC-5 remained comparable to sorafenib. The synthetic derivative 5r, thus, possessed 5.2-time higher selectivity index (SI) than that of sorafenib. Molecular docking studies revealed an efficient interaction of 5r at the same sorafenib's binding region in both B-Raf and VEGFR-2 with lower binding energies than those of sorafenib, consistent with its cytotoxic effect. Furthermore, 5r was proven to induce apoptosis in a dose-dependent manner similar to sorafenib. In addition, the prediction using SwissADME suggested that 5r possessed appropriate drug properties conforming to Veber's studies. These findings revealed that the newly designed meta-ureidophenoxy-1,2,3-triazole hybrid scaffold was a promising structural feature for an efficient inhibition of HepG2. Moreover, derivative 5r emerged as a promising candidate for further development as a targeted anti-cancer agent for hepatocellular carcinoma (HCC). | Compounds with activity <= 10uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation._||_Journal: Bioorg Med Chem_||_Year: 2022_||_Volume: 74_||_First Page: 117048_||_Last Page: 117048_||_DOI: 10.1016/j.bmc.2022.117048_||_Target ChEMBL ID: CHEMBL395_||_ChEMBL Target Name: HepG2_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5217717 | 20230629 | 20230629 | 216239|168298100|168298141|168298193|168298232|168298253|168298388|168298412|168298432|168298460|168298503|168298517|168298665|168298703|168298709|168298736|168298750|168298764|168298938|168298941|168299185|168299300|168299454|168299498|168299506|168299546|168299553|168299603|168299672|168299677|168299723|168299803 | 103420820|482088480|482088539|482088619|482088673|482088703|482088888|482088919|482088945|482088985|482089042|482089058|482089257|482089314|482089320|482089363|482089382|482089399|482089646|482089650|482089982|482090142|482090353|482090409|482090423|482090481|482090491|482090554|482090661|482090669|482090727|482090844 | null | null | null | Curation Efforts|Research and Development | 36270111 | 0 | null | null | 9606 | null | null | 32 | 30 | null | null | null |
1918196 | Confirmatory | Cytotoxicity against human MRC5 cells assessed as inhibition of cell viability incubated for 72 hrs by MTT assay | Title: meta-Ureidophenoxy-1,2,3-triazole hybrid as a novel scaffold for promising HepG2 hepatocellular carcinoma inhibitors: Synthesis, biological evaluation and molecular docking studies._||_Abstract: Thirty-one meta-ureidophenoxymethyl-1,2,3-triazole derivatives were designed and synthesized via nucleophilic addition, nucleophilic substitution and copper-catalyzed azide-alkyne cycloaddition (CuAAC). The evaluation of their cytotoxicity using MTT assay indicated that almost all derivatives exhibited significantly superior inhibitory activity against hepatocellular carcinoma cell line HepG2 compared to the parental molecule sorafenib (1). Among the series, 5r was the most potent anti-HepG2 agent with IC<sub>50</sub> = 1.04 µM, which was almost 5-fold more active than sorafenib (IC<sub>50</sub> = 5.06 µM), while the cytotoxic activity against human embryonal lung fibroblast cell line MRC-5 remained comparable to sorafenib. The synthetic derivative 5r, thus, possessed 5.2-time higher selectivity index (SI) than that of sorafenib. Molecular docking studies revealed an efficient interaction of 5r at the same sorafenib's binding region in both B-Raf and VEGFR-2 with lower binding energies than those of sorafenib, consistent with its cytotoxic effect. Furthermore, 5r was proven to induce apoptosis in a dose-dependent manner similar to sorafenib. In addition, the prediction using SwissADME suggested that 5r possessed appropriate drug properties conforming to Veber's studies. These findings revealed that the newly designed meta-ureidophenoxy-1,2,3-triazole hybrid scaffold was a promising structural feature for an efficient inhibition of HepG2. Moreover, derivative 5r emerged as a promising candidate for further development as a targeted anti-cancer agent for hepatocellular carcinoma (HCC). | Compounds with activity <= 10uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation._||_Journal: Bioorg Med Chem_||_Year: 2022_||_Volume: 74_||_First Page: 117048_||_Last Page: 117048_||_DOI: 10.1016/j.bmc.2022.117048_||_Target ChEMBL ID: CHEMBL614181_||_ChEMBL Target Name: MRC5_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5217718 | 20230629 | 20230629 | 216239|168298100|168298141|168298253|168298460|168298750|168298764|168299454|168299498|168299546|168299677|168299723 | 103420820|482088480|482088539|482088703|482088985|482089382|482089399|482090353|482090409|482090481|482090669|482090727 | null | Toxicity | null | Curation Efforts|Research and Development | 36270111 | 0 | null | null | 9606 | null | null | 12 | 5 | null | null | null |
1918197 | Literature-derived | Selectivity index, ratio of IC50 for cytotoxicity against human MRC5 cells to IC50 for anticancer activity against human HepG2 cells | Title: meta-Ureidophenoxy-1,2,3-triazole hybrid as a novel scaffold for promising HepG2 hepatocellular carcinoma inhibitors: Synthesis, biological evaluation and molecular docking studies._||_Abstract: Thirty-one meta-ureidophenoxymethyl-1,2,3-triazole derivatives were designed and synthesized via nucleophilic addition, nucleophilic substitution and copper-catalyzed azide-alkyne cycloaddition (CuAAC). The evaluation of their cytotoxicity using MTT assay indicated that almost all derivatives exhibited significantly superior inhibitory activity against hepatocellular carcinoma cell line HepG2 compared to the parental molecule sorafenib (1). Among the series, 5r was the most potent anti-HepG2 agent with IC<sub>50</sub> = 1.04 µM, which was almost 5-fold more active than sorafenib (IC<sub>50</sub> = 5.06 µM), while the cytotoxic activity against human embryonal lung fibroblast cell line MRC-5 remained comparable to sorafenib. The synthetic derivative 5r, thus, possessed 5.2-time higher selectivity index (SI) than that of sorafenib. Molecular docking studies revealed an efficient interaction of 5r at the same sorafenib's binding region in both B-Raf and VEGFR-2 with lower binding energies than those of sorafenib, consistent with its cytotoxic effect. Furthermore, 5r was proven to induce apoptosis in a dose-dependent manner similar to sorafenib. In addition, the prediction using SwissADME suggested that 5r possessed appropriate drug properties conforming to Veber's studies. These findings revealed that the newly designed meta-ureidophenoxy-1,2,3-triazole hybrid scaffold was a promising structural feature for an efficient inhibition of HepG2. Moreover, derivative 5r emerged as a promising candidate for further development as a targeted anti-cancer agent for hepatocellular carcinoma (HCC). | Journal: Bioorg Med Chem_||_Year: 2022_||_Volume: 74_||_First Page: 117048_||_Last Page: 117048_||_DOI: 10.1016/j.bmc.2022.117048 | 43 | ChEMBL | CHEMBL5217719 | 20230629 | 20230629 | 216239|168298100|168298141|168298253|168298460|168298750|168298764|168299454|168299498|168299546|168299677|168299723 | 103420820|482088480|482088539|482088703|482088985|482089382|482089399|482090353|482090409|482090481|482090669|482090727 | null | Toxicity | null | Curation Efforts|Research and Development | 36270111 | 0 | null | null | 9606 | null | null | 12 | null | null | null | null |
1918198 | Literature-derived | Potency index, ratio of Sorafenib IC50 to test compound IC50 for anticancer activity against human HepG2 cells assessed as inhibition of cell viability incubated for 72 hrs by MTT assay | Title: meta-Ureidophenoxy-1,2,3-triazole hybrid as a novel scaffold for promising HepG2 hepatocellular carcinoma inhibitors: Synthesis, biological evaluation and molecular docking studies._||_Abstract: Thirty-one meta-ureidophenoxymethyl-1,2,3-triazole derivatives were designed and synthesized via nucleophilic addition, nucleophilic substitution and copper-catalyzed azide-alkyne cycloaddition (CuAAC). The evaluation of their cytotoxicity using MTT assay indicated that almost all derivatives exhibited significantly superior inhibitory activity against hepatocellular carcinoma cell line HepG2 compared to the parental molecule sorafenib (1). Among the series, 5r was the most potent anti-HepG2 agent with IC<sub>50</sub> = 1.04 µM, which was almost 5-fold more active than sorafenib (IC<sub>50</sub> = 5.06 µM), while the cytotoxic activity against human embryonal lung fibroblast cell line MRC-5 remained comparable to sorafenib. The synthetic derivative 5r, thus, possessed 5.2-time higher selectivity index (SI) than that of sorafenib. Molecular docking studies revealed an efficient interaction of 5r at the same sorafenib's binding region in both B-Raf and VEGFR-2 with lower binding energies than those of sorafenib, consistent with its cytotoxic effect. Furthermore, 5r was proven to induce apoptosis in a dose-dependent manner similar to sorafenib. In addition, the prediction using SwissADME suggested that 5r possessed appropriate drug properties conforming to Veber's studies. These findings revealed that the newly designed meta-ureidophenoxy-1,2,3-triazole hybrid scaffold was a promising structural feature for an efficient inhibition of HepG2. Moreover, derivative 5r emerged as a promising candidate for further development as a targeted anti-cancer agent for hepatocellular carcinoma (HCC). | Journal: Bioorg Med Chem_||_Year: 2022_||_Volume: 74_||_First Page: 117048_||_Last Page: 117048_||_DOI: 10.1016/j.bmc.2022.117048_||_Target ChEMBL ID: CHEMBL395_||_ChEMBL Target Name: HepG2_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5217720 | 20230629 | 20230629 | 168298750|168299723 | 482089382|482090727 | null | null | null | Curation Efforts|Research and Development | 36270111 | 0 | null | null | 9606 | null | null | 2 | null | null | null | null |
1918199 | Literature-derived | Induction of apoptosis in human HepG2 cells at 1 uM incubated for 72 hrs by Annexin V-FITC/PI staining based flow cytometry | Title: meta-Ureidophenoxy-1,2,3-triazole hybrid as a novel scaffold for promising HepG2 hepatocellular carcinoma inhibitors: Synthesis, biological evaluation and molecular docking studies._||_Abstract: Thirty-one meta-ureidophenoxymethyl-1,2,3-triazole derivatives were designed and synthesized via nucleophilic addition, nucleophilic substitution and copper-catalyzed azide-alkyne cycloaddition (CuAAC). The evaluation of their cytotoxicity using MTT assay indicated that almost all derivatives exhibited significantly superior inhibitory activity against hepatocellular carcinoma cell line HepG2 compared to the parental molecule sorafenib (1). Among the series, 5r was the most potent anti-HepG2 agent with IC<sub>50</sub> = 1.04 µM, which was almost 5-fold more active than sorafenib (IC<sub>50</sub> = 5.06 µM), while the cytotoxic activity against human embryonal lung fibroblast cell line MRC-5 remained comparable to sorafenib. The synthetic derivative 5r, thus, possessed 5.2-time higher selectivity index (SI) than that of sorafenib. Molecular docking studies revealed an efficient interaction of 5r at the same sorafenib's binding region in both B-Raf and VEGFR-2 with lower binding energies than those of sorafenib, consistent with its cytotoxic effect. Furthermore, 5r was proven to induce apoptosis in a dose-dependent manner similar to sorafenib. In addition, the prediction using SwissADME suggested that 5r possessed appropriate drug properties conforming to Veber's studies. These findings revealed that the newly designed meta-ureidophenoxy-1,2,3-triazole hybrid scaffold was a promising structural feature for an efficient inhibition of HepG2. Moreover, derivative 5r emerged as a promising candidate for further development as a targeted anti-cancer agent for hepatocellular carcinoma (HCC). | Journal: Bioorg Med Chem_||_Year: 2022_||_Volume: 74_||_First Page: 117048_||_Last Page: 117048_||_DOI: 10.1016/j.bmc.2022.117048_||_Target ChEMBL ID: CHEMBL395_||_ChEMBL Target Name: HepG2_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5217721 | 20230629 | 20230629 | 216239|168299723 | 103420820|482090727 | null | null | null | Curation Efforts|Research and Development | 36270111 | 0 | null | null | 9606 | null | null | 2 | null | null | null | null |
1918200 | Literature-derived | Induction of apoptosis in human HepG2 cells at 5 uM incubated for 72 hrs by Annexin V-FITC/PI staining based flow cytometry | Title: meta-Ureidophenoxy-1,2,3-triazole hybrid as a novel scaffold for promising HepG2 hepatocellular carcinoma inhibitors: Synthesis, biological evaluation and molecular docking studies._||_Abstract: Thirty-one meta-ureidophenoxymethyl-1,2,3-triazole derivatives were designed and synthesized via nucleophilic addition, nucleophilic substitution and copper-catalyzed azide-alkyne cycloaddition (CuAAC). The evaluation of their cytotoxicity using MTT assay indicated that almost all derivatives exhibited significantly superior inhibitory activity against hepatocellular carcinoma cell line HepG2 compared to the parental molecule sorafenib (1). Among the series, 5r was the most potent anti-HepG2 agent with IC<sub>50</sub> = 1.04 µM, which was almost 5-fold more active than sorafenib (IC<sub>50</sub> = 5.06 µM), while the cytotoxic activity against human embryonal lung fibroblast cell line MRC-5 remained comparable to sorafenib. The synthetic derivative 5r, thus, possessed 5.2-time higher selectivity index (SI) than that of sorafenib. Molecular docking studies revealed an efficient interaction of 5r at the same sorafenib's binding region in both B-Raf and VEGFR-2 with lower binding energies than those of sorafenib, consistent with its cytotoxic effect. Furthermore, 5r was proven to induce apoptosis in a dose-dependent manner similar to sorafenib. In addition, the prediction using SwissADME suggested that 5r possessed appropriate drug properties conforming to Veber's studies. These findings revealed that the newly designed meta-ureidophenoxy-1,2,3-triazole hybrid scaffold was a promising structural feature for an efficient inhibition of HepG2. Moreover, derivative 5r emerged as a promising candidate for further development as a targeted anti-cancer agent for hepatocellular carcinoma (HCC). | Journal: Bioorg Med Chem_||_Year: 2022_||_Volume: 74_||_First Page: 117048_||_Last Page: 117048_||_DOI: 10.1016/j.bmc.2022.117048_||_Target ChEMBL ID: CHEMBL395_||_ChEMBL Target Name: HepG2_||_ChEMBL Target Type: CELL-LINE - Target is a specific cell-line_||_Relationship Type: N - Non-molecular target assigned_||_Confidence: Target assigned is non-molecular | 43 | ChEMBL | CHEMBL5217722 | 20230629 | 20230629 | 216239|168299723 | 103420820|482090727 | null | null | null | Curation Efforts|Research and Development | 36270111 | 0 | null | null | 9606 | null | null | 2 | 2 | null | null | null |
1919092 | Confirmatory | Biochemical Assay from US Patent US11524945: 'Compounds for treating ILK-mediated diseases' | Thus, while these compounds were extensively used in studying ILK-mediated cellular and disease processes, their reported inhibitory effects are probably due to unknown artifacts or indirect binding events. Next, we turned our attention to previously reported studies on kinase profiling and quantitative chemical proteomics. These studies suggested that a widely known lung cancer drug erlotinib, which targets EGFR, might also bind to ILK as an off target. By performing a robust fluorescence-based binding assay, we found that the FDA approved drug Erlotinib (TARCEVA) indeed binds potently to purified recombinant ILK at KD 0.43M, which is very close to the affinity of Erlotinib to EGFR measured at the same experimental conditions (KD 0.31 μM). Another erlotinib-like EGFR inhibitor Gefitinib exhibited 10-fold weaker binding affinity to ILK (KD 4.51 μM) yet 3-fold stronger affinity to EGFR (KD 0.11 μM) than erlotinib. | Compounds with any of Ki, IC50, Kd, or EC50 activity value <= 10uM are labeled as 'Active'._||_If multiple measurements are available for a given compound, it is labeled as 'Active' if any of the measurements meet the criterion. Activity values are checked in the order of Ki, IC50, Kd, and EC50. The first entry that meets the above activity threshold is used to determine 'Standard Type', 'Standard Relation', and 'PubChem Standard Value'. Otherwise, the first non-empty entry will be used to set those values. | 7 | BindingDB | BindingDB_10997_1 | 20231017 | 20231017 | 176870|71750333|156290307|156290308|156290315|156290316|156290321|156290367|156290638|156290805 | 8035065|475952607|475952608|475952609|475952610|475952611|475952612|475952613|475952614|475952615 | 1956|3611 | Biochemical | P00533|Q13418 | Curation Efforts|Research and Development | null | 0 | 2.7.10.1|2.7.11.1 | P00533|Q13418 | 9606 | null | null | 10 | 9 | null | null | null |
1919120 | Confirmatory | hERG Assay from US Patent US11530208: 'Imidazo[4,5-C]pyridine derived SSAO inhibitors' | Compounds of the invention were tested for inhibition of the human ether a go-go related gene (hERG) K+ channel using IonWorks patch clamp electrophysiology. 8 Point concentration-response curves were generated on two occasions using 3-fold serial dilutions from the maximum assay concentration (11 uM). Electrophysiological recordings were made from a Chinese Hamster Lung cell line stably expressing the full length hERG channel. Single cell ion currents were measured in the perforated patch clamp configuration (100 ug/mL amphoterocin) at RT using an IonWorks Quattro instrument. The internal solution contained 140 mM KCl, 1 mM MgCl2, 1 mM EGTA and 20 mM HEPES and was buffered to pH 7.3. The external solution contained 138 mM NaCl, 2.7 mM KCl, 0.9 mM CaCl2, 0.5 mM MgCl2, 8 mM Na2HPO4 and 1.5 mM KH2PO4, and was buffered to pH 7.3. Cells were clamped at a holding potential of 70 mV for 30 s and then stepped to +40 mV for 1 s. This was followed by a hyperpolarising step of 1 s to 30 mV to evoke the hERG tail current. This sequence was repeated 5 times at a frequency of 0.25 Hz. Currents were measured from the tail step at the 5th pulse, and referenced to the holding current. Compounds were incubated for 6-7 min prior to a second measurement of the hERG signal using an identical pulse train. A minimum of 17 cells were required for each pIC50 curve fit. | Compounds with any of Ki, IC50, Kd, or EC50 activity value <= 10uM are labeled as 'Active'._||_If multiple measurements are available for a given compound, it is labeled as 'Active' if any of the measurements meet the criterion. Activity values are checked in the order of Ki, IC50, Kd, and EC50. The first entry that meets the above activity threshold is used to determine 'Standard Type', 'Standard Relation', and 'PubChem Standard Value'. Otherwise, the first non-empty entry will be used to set those values. | 7 | BindingDB | BindingDB_11014_2 | 20231017 | 20231017 | 118961547|129237845 | 475954990|475954992 | 3757 | null | Q12809 | Curation Efforts|Research and Development | null | 0 | null | Q12809 | 9606 | null | null | 2 | 1 | null | null | null |
1919627 | Confirmatory | In Vitro Assay from US Patent US11718589: 'Compositions and methods of modulating short-chain dehydrogenase' | This Example provides data on two groups (Table 1 and Table 2) of structural analogues of identified 15-PGDH inhibitors. Data provided is the IC50 of each compound for inhibiting enzymatic activity of recombinant 15-PGDH in an in vitro assay. Recombinant 15-PGDH is human unless otherwise specified. 15-PGDH inhibitors described herein can provide a pharmacologic method for elevating prostaglandin levels in tissue. Known activities of prostaglandins include promoting hair growth, promoting skin pigmentation, and promoting skin darkening or the appearance of skin tanning. Known activities of prostaglandins also include ameliorating pulmonary artery hypertension. 15-PGDH inhibitors described herein may also be utilized to increase tissue stem cell numbers for purposes that would include increasing resistance to tissue damage by radiation, increasing resistance to environmental exposures to radiation, increasing stem cell numbers to increase fitness of bone marrow or other types of transplantation (through either in vivo exposure to 15-PGDH inhibitors described herein to increase stem cell numbers prior to harvest of a transplanted tissue, or through ex vivo exposure of a harvested tissue prior to transplant into a recipient host, or through treatment of the graft recipient). | Compounds with any of Ki, IC50, Kd, or EC50 activity value <= 10uM are labeled as 'Active'._||_If multiple measurements are available for a given compound, it is labeled as 'Active' if any of the measurements meet the criterion. Activity values are checked in the order of Ki, IC50, Kd, and EC50. The first entry that meets the above activity threshold is used to determine 'Standard Type', 'Standard Relation', and 'PubChem Standard Value'. Otherwise, the first non-empty entry will be used to set those values. | 7 | BindingDB | BindingDB_11389_1 | 20231017 | 20231017 | 148184|629852|1046498|1046563|1069833|1069843|1111003|1111004|1113948|1113977|1230006|1230007|1244790|2215311|2872139|3107662|3107663|3107665|3107670|3684054|4158455|4344590|4422418|4581995|4582762|5261755|5261756|5261757|43853055|110766080|135290842|135290851|135290857|135290858|135290861|135300255|135300256|135300257|135300258|135300259|135300261|135300262|135300263|135300264|135300265|135300266|135300267|135300268|135300269|135300270|135300271|135300272|135300273|135300277|135300278|135300281|135300284|135300285|135300286|135300288|135300289|135300290|135300329|135300330|135300331|135300332|135300333|135300334|135300337|135300338|135300340|135300342|135300343|135300344|135300345|135300347|135300348|135300349|135300352|135300353|135300354|135300355|135300356|135300357|135300358|135300359|135300362|135300365|135300368|135300371|135300372|135300374|135300376|135300377|135300381|135300382|135300384|135300385|135300386|135300387|135300388|135300390|135300391|135300392|135300395|135300396|135300398|135300400|135300401|135300402|135300404|135300405|135300406|135300407|135300408|135300409|135300410|135300411|135300412|135300414|135300415|135300416|135300417|135300418|135300419|135300422|135300426|135300429|135300430|135300431|135300433|135300434|135300435|135300436|135300437|135300438|135300439|135300445|135300446|135300447|135300448|135300449|135300450|135300451|135300452|135300453|135300461|135300462|135300463|135300464|137281322|137281323|146476157|146476159|146476161|146476162|146476163|146476164|146476165|146476167|146476168|146476170|146476178|168489811 | 103991908|252629270|252662401|482618457|482618458|482618459|482618460|482618461|482618462|482618463|482618464|482618465|482618466|482618467|482618468|482618469|482618470|482618471|482618472|482618473|482618474|482618475|482618476|482618477|482618478|482618479|482618480|482618481|482618482|482618483|482618484|482618485|482618486|482618487|482618488|482618489|482618491|482618492|482618493|482618494|482618495|482618496|482618497|482618498|482618499|482618500|482618501|482618502|482618503|482618504|482618506|482618507|482618508|482618509|483621744|483621745|483621746|483621747|483621748|483621749|483621750|483621751|483621752|483621753|483621754|483621755|483621756|483621757|483621758|483621759|483621760|483621761|483621762|483621763|483621764|483621765|483621766|483621767|483621768|483621769|483621770|483621771|483621772|483621773|483621774|483621775|483621776|483621777|483621778|483621779|483621780|483621781|483621782|483621783|483621784|483621785|483621786|483621787|483621788|483621789|483621790|483621791|483621792|483621793|483621794|483621795|483621796|483621797|483621798|483621799|483621800|483621801|483621802|483621803|483621804|483621805|483621806|483621807|483621808|483621809|483621810|483621811|483621812|483621813|483621814|483621815|483621816|483621817|483621819|483621820|483621821|483621832|483621833|483621834|483621836|483621838|483621843|483621845|483621846|483621849|483621850|483621851|483621852|483621853|483621854|483621855|483621856|483621858|483621859|483621862|483621864|483621868|483621878|483621880|483621884|483621892|483621897|483621901|483621902|483621903|483621904|483621905|483621906|483621907 | 3248 | In vitro | P15428 | Curation Efforts|Research and Development | null | 0 | 1.1.1.-|1.1.1.141|1.1.1.232 | P15428 | 9606 | null | null | 164 | 124 | null | null | null |
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