Identification of benzothiophene amides as potent inhibitors of human nicotinamide phosphoribosyltransferase

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.

A series of novel benzothiophene Nampt inhibitors were designed and synthesized. Compounds 16b showed good Nampt inhibitory activity and in vitro antitumor activity.Figure optionsDownload as PowerPoint slide