284672-99-7Relevant academic research and scientific papers
Fragment-based design of 3-aminopyridine-derived amides as potent inhibitors of human nicotinamide phosphoribosyltransferase (NAMPT)
Dragovich, Peter S.,Zhao, Guiling,Baumeister, Timm,Bravo, Brandon,Giannetti, Anthony M.,Ho, Yen-Ching,Hua, Rongbao,Li, Guangkun,Liang, Xiaorong,Ma, Xiaolei,O'Brien, Thomas,Oh, Angela,Skelton, Nicholas J.,Wang, Chengcheng,Wang, Weiru,Wang, Yunli,Xiao, Yang,Yuen, Po-Wai,Zak, Mark,Zhao, Qiang,Zheng, Xiaozhang
, p. 954 - 962 (2014/02/14)
The fragment-based identification of two novel and potent biochemical inhibitors of the nicotinamide phosphoribosyltransferase (NAMPT) enzyme is described. These compounds (51 and 63) incorporate an amide moiety derived from 3-aminopyridine, and are thus structurally distinct from other known anti-NAMPT agents. Each exhibits potent inhibition of NAMPT biochemical activity (IC 50 = 19 and 15 nM, respectively) as well as robust antiproliferative properties in A2780 cell culture experiments (IC50 = 121 and 99 nM, respectively). However, additional biological studies indicate that only inhibitor 51 exerts its A2780 cell culture effects via a NAMPT-mediated mechanism. The crystal structures of both 51 and 63 in complex with NAMPT are also independently described.
