As of 2014, a Phase 1 clinical trial to assess the safety profile in human is planned by the Howard Hughes Medical Institute. NITD246 and NITD609: Also belonged to the class of spiroindolone and target the ATP4 protein.On the basis of molecular docking outcomes, compounds 3j, 4b, 4h, 4m were exhibited selectivity towards PfLDH. The post docking analysis displayed stable dynamic behavior of all the selected compounds compared to Chloroquine. The end state thermodynamics analysis stated 3j compound as a selective and potent PfLDH inhibitor. New targets
Targeting Plasmodium liver-stage parasites selectively is emerging as an alternative strategy in the face of resistance to the latest frontline combination therapies against blood stages of the parasite.In a research conducted in 2019, using experimental analysis with knockout (KO) mutants of Plasmodium berguei the authors were able to identify genes that are potentially essential in the liver stage. Moreover, they generated a computational model to analyse pre–erytrocytic development and liver–stage metabolism. Combining both methods they identified seven metabolic subsystems that become essential compared to the blood stage. Some of these metabolic pathways are fatty acid synthesis and elongation, tricarboxylic acid, amino acid and heme metabolism among others.Specifically, they studied 3 subsystems: fatty acid synthesis and elongation, and amino sugar biosynthesis. For the first two pathways they demonstrated a clear dependence of the liver stage on its own fatty acid metabolism.They proved for the first time the critical role of amino sugar biosynthesis in the liver stage of P. berghei.
Emicizumab (trade name Hemlibra) is a humanized bispecific antibody for the treatment of haemophilia A, developed by Genentech and Chugai (a subsidiary of Roche). A Phase I clinical trial found that it was well tolerated by healthy subjects.In November 2017, it was approved in the United States for treatment of haemophilia A in those who had developed resistance to other treatments. It was subsequently approved by the US FDA in April 2018 under the breakthrough therapy designation for treatment of haemophila A in those who have not developed resistance to other treatments. The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication. Mechanism of action
Emicizumab binds to both the activated coagulation factor IX and to factor X, mediating the activation of the latter. This is normally the function of coagulation factor VIII, which is missing in haemophilia A patients. References
External links
"Emicizumab". Drug Information Portal. U.S. National Library of Medicine.