Dual NAMPT/HDAC Inhibitors as a New Strategy for Multitargeting Antitumor Drug Discovery

  • ACS Med Chem Lett. 2017 Dec 14;9(1):34-38. doi: 10.1021/acsmedchemlett.7b00414.
Wei Chen  1 ,  Guoqiang Dong  1 ,  Ying Wu  1 ,  Wannian Zhang  1 ,  Chaoyu Miao  1 ,  Chunquan Sheng  1
Affiliations
  • 1. School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
PMID: 29348808 DOI: 10.1021/acsmedchemlett.7b00414
Abstract

Novel dual nicotinamide phosphoribosyltransferase (NAMPT) and histone deacetylase (HDAC) inhibitors were designed by a pharmacophore fusion approach. The thiazolocarboxamide inhibitors were highly active for both targets. In particular, compound 7f (NAMPT IC50 = 15 nM, HDAC1 IC50 = 2 nM) showed potent in vivo antitumor efficacy in the HCT116 xenograft model. The study offers a new strategy for multitarget antitumor drug discovery by simultaneously acting on Cancer metabolism and Epigenetics.

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