A perspective on medicinal chemistry approaches towards adenomatous polyposis coli and Wnt signal based colorectal cancer inhibitors.
Phull MS, Jadav SS, Gundla R, Mainkar PS.
Colorectal cancer (CRC) is one of the major causes of carcinogenic mortality in numbers only after lung and breast cancers. The mutations in adenomatous polyposis coli (APC) gene leads to formation of colorectal polyps in the colonic region and which develop as a malignant tumour upon coalition with patient related risk factors. The protein-protein interaction (PPI) of APC with Asef (A Rac specific guanine nucleotide exchange factor) overwhelms the patient's conditions by rapidly spreading in the entire colorectal region. Most mutations in APC gene occur in mutated cluster region (MCR), where it specifically binds with the cytosolic β-catenin to regulate the Wnt signalling pathway required for CRC cell adhesion, invasion, progression, differentiation and stemness in initial cell cycle phages. The current broad spectrum perspective is attempted to elaborate the sources of identification, development of selective APC inhibitors by targeting emopamil-binding protein (EBP) & dehydrocholesterol reductase-7 & 24 (DHCR-7 & 24); APC-Asef, β-catenin/APC, Wnt/β-catenin, β-catenin/TCF4 PPI inhibitors with other vital Wnt signal cellular proteins and APC/Pol-β interface of colorectal cancer. In this context, this perspective would serve as a platform for design of new medicinal agents by targeting cellular essential components which could accelerate anti-colorectal potential candidates.