Send to

Choose Destination
See comment in PubMed Commons below
Bioorg Med Chem Lett. 2014 Feb 1;24(3):954-62. doi: 10.1016/j.bmcl.2013.12.062. Epub 2013 Dec 21.

Fragment-based design of 3-aminopyridine-derived amides as potent inhibitors of human nicotinamide phosphoribosyltransferase (NAMPT).

Author information

  • 1Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA. Electronic address:
  • 2Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
  • 3Forma Therapeutics, Inc., 500 Arsenal Street, Watertown, MA 02472, USA.
  • 4Pharmaron Beijing, Co. Ltd., 6 Taihe Road, BDA, Beijing 100176, PR China.
  • 5Crown Bioscience, Science & Technology Innovation Park, No.6 Beijing West Road, Taicang City, Jiangsu Province, PR China.


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 (IC50=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.

Copyright © 2013 Elsevier Ltd. All rights reserved.


Fragment-based design; NAMPT; Nicotinamide phosphoribosyltransferase; Structure-based design; Surface plasmon resonance; X-ray crystal structure

[PubMed - indexed for MEDLINE]

LinkOut - more resources

Full Text Sources

Other Literature Sources

Chemical Information


PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk