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.

中文翻译：

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NAMPT / HDAC双重抑制剂作为多靶点抗肿瘤药物发现的新策略

通过药效基团融合方法设计了新型双重烟酰胺磷酸核糖基转移酶（NAMPT）和组蛋白脱乙酰基酶（HDAC）抑制剂。噻唑甲酰胺抑制剂对两个靶均具有高活性。特别地，化合物7f（NAMPT IC ₅₀ = 15 nM，HDAC1 IC ₅₀ = 2 nM）在HCT116异种移植模型中显示出强大的体内抗肿瘤功效。该研究通过同时作用于癌症的新陈代谢和表观遗传学，为发现多靶点抗肿瘤药物提供了新的策略。