Wu Ying, Wang Lei, Huang Yahui, Chen Shuqiang, Wu Shanchao, Dong Guoqiang, Sheng Chunquan
Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.
ACS Med Chem Lett. 2019 Dec 13;11(1):40-44. doi: 10.1021/acsmedchemlett.9b00407. eCollection 2020 Jan 9.
Chidamide is a histone deacetylase (HDAC) inhibitor that is currently used to treat cutaneous T-cell lymphoma in clinic. Herein nicotinamide phosphoribosyltransferase (NAMPT) was identified to be a new target of chidamide on the basis of the pharmacophore analysis, molecular docking, biological assays, inhibitor design, and structure-activity relationship study. The polypharmacology of chidamide will provide important information for better understanding its antitumor mechanism. Also, design of dual NAMPT/HDAC inhibitors may serve as an effective strategy to develop novel antitumor agents.
西达本胺是一种组蛋白去乙酰化酶（HDAC）抑制剂，目前在临床上用于治疗皮肤T细胞淋巴瘤。在此，基于药效团分析、分子对接、生物学试验、抑制剂设计和构效关系研究，烟酰胺磷酸核糖转移酶（NAMPT）被确定为西达本胺的一个新靶点。西达本胺的多药理学将为更好地理解其抗肿瘤机制提供重要信息。此外，设计双靶点NAMPT/HDAC抑制剂可能是开发新型抗肿瘤药物的有效策略。
