Chen Wei, Dong Guoqiang, Wu Ying, Zhang Wannian, Miao Chaoyu, Sheng Chunquan
School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
ACS Med Chem Lett. 2017 Dec 14;9(1):34-38. doi: 10.1021/acsmedchemlett.7b00414. eCollection 2018 Jan 11.
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 (NAMPT IC = 15 nM, HDAC1 IC = 2 nM) showed potent 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.
通过药效团融合方法设计了新型双功能烟酰胺磷酸核糖转移酶（NAMPT）和组蛋白去乙酰化酶（HDAC）抑制剂。噻唑甲酰胺抑制剂对这两个靶点均具有高活性。特别是化合物（NAMPT IC = 15 nM，HDAC1 IC = 2 nM）在HCT116异种移植模型中显示出强效的抗肿瘤功效。该研究为通过同时作用于癌症代谢和表观遗传学来发现多靶点抗肿瘤药物提供了一种新策略。
