Dong, Guoqiang; Chen, Wei; Wang, Xia; Yang, Xinglin; Xu, Tianying; Wang, Pei; Zhang, Wannian; Rao, Yu; Miao, Chaoyu; Sheng, Chunquan published the artcile< Small Molecule Inhibitors Simultaneously Targeting Cancer Metabolism and Epigenetics: Discovery of Novel Nicotinamide Phosphoribosyltransferase (NAMPT) and Histone Deacetylase (HDAC) Dual Inhibitors>, Synthetic Route of 56622-54-9, the main research area is preparation NAMPT HDAC dual inhibitor cancer; antitumor preparation nicotinamide phosphoribosyltransferase histone deacetylase inhibitor.
Cancer metabolism and epigenetics are among the most intensely pursued research areas in anticancer drug discovery. Here we report the first small mols. that simultaneously inhibit nicotinamide phosphoribosyltransferase (NAMPT)and histone deacetylase (HDAC), two important targets of cancer metabolism and epigenetics, resp. Through iterative structure-based drug design, chem. synthesis, and biol. assays, a highly potent dual NAMPT and HDAC inhibitor was successfully identified. Compound 35 possessed excellent and balanced activities against both NAMPT (IC50 = 31 nM) and HDAC1 (IC50 = 55 nM). It could effectively induce cell apoptosis and autophagy and ultimately led to cell death. Importantly, compound 35 showed excellent in vivo antitumor efficacy in the HCT116 xenograft model. This proof-of-concept study demonstrates the feasibility of discovering an inhibitor targeting cancer metabolism and epigenetics and provides an efficient strategy for multitarget antitumor drug discovery.
Journal of Medicinal Chemistry published new progress about Antitumor agents. 56622-54-9 belongs to class pyridine-derivatives, and the molecular formula is C7H10N2, Synthetic Route of 56622-54-9.