Identification of benzothiophene amides as potent inhibitors of human nicotinamide phosphoribosyltransferase

Bioorg Med Chem Lett. 2016 Feb 1;26(3):765-768. doi: 10.1016/j.bmcl.2015.12.101. Epub 2015 Dec 29.


Nicotinamide phosphoribosyltransferase (Nampt) is an attractive therapeutic target for cancer. A Nampt inhibitor with novel benzothiophene scaffold was discovered by high throughput screening. Herein the structure-activity relationship of the benzothiophene Nampt inhibitor was investigated. Several new inhibitors demonstrated potent activity in both biochemical and cell-based assays. In particular, compound 16b showed good Nampt inhibitory activity (IC50=0.17 μM) and in vitro antitumor activity (IC50=3.9 μM, HepG2 cancer cell line). Further investigation indicated that compound 16b could efficiently induce cancer cell apoptosis. Our findings provided a good starting point for the discovery of novel antitumor agents.

Keywords: Antiproliferative activity; Nampt inhibitors; Structure–activity relationship.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemical synthesis
  • Amides / chemistry*
  • Amides / pharmacology
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Binding Sites
  • Catalytic Domain
  • Cell Line, Tumor
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology
  • Hep G2 Cells
  • Humans
  • Molecular Docking Simulation
  • Nicotinamide Phosphoribosyltransferase / antagonists & inhibitors*
  • Nicotinamide Phosphoribosyltransferase / metabolism
  • Structure-Activity Relationship
  • Thiophenes / chemistry*


  • Amides
  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Thiophenes
  • benzothiophene
  • Nicotinamide Phosphoribosyltransferase