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

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.

SUBMITTER: Chen W

PROVIDER: S-EPMC5767891 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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

Chen Wei W Dong Guoqiang G Wu Ying Y Zhang Wannian W Miao Chaoyu C Sheng Chunquan C

ACS medicinal chemistry letters 20171214 1

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 ca ...[more]

PMID: 29348808

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