Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10594884 | Bioorganic & Medicinal Chemistry Letters | 2014 | 9 Pages |
Abstract
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 (IC50Â =Â 19 and 15Â nM, respectively) as well as robust antiproliferative properties in A2780 cell culture experiments (IC50Â =Â 121 and 99Â 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.
Keywords
Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Peter S. Dragovich, Guiling Zhao, Timm Baumeister, Brandon Bravo, Anthony M. Giannetti, Yen-Ching Ho, Rongbao Hua, Guangkun Li, Xiaorong Liang, Xiaolei Ma, Thomas O'Brien, Angela Oh, Nicholas J. Skelton, Chengcheng Wang, Weiru Wang, Yunli Wang,