Chen Ya-Dong, Jiang Yong-Jun, Zhou Jian-Wei, Yu Qing-Sen, You Qi-Dong
Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
J Mol Graph Model. 2008 Apr;26(7):1160-8. doi: 10.1016/j.jmgm.2007.10.007. Epub 2007 Oct 23.
Histone deacetylases (HDACs) enzyme plays a significant role in transcriptional regulation by modifying the core histones of the nucleosome. It has emerged as an important therapeutic target for the treatment of cancer and other diseases. Inhibitors of HDACs become a new class of anticancer agents and have provoked much interest amongst pharmacologists and cancer researchers. To facilitate the discovery of specific HDACs inhibitors, a 3D chemical-feature-based QSAR pharmacophore model was developed and was well consistent with the structure-functional requirements for the binding of the HDAC inhibitors. Using this model, the interactions between the benzamide MS-275 and HDAC were explored. The result showed that the type and spatial location of chemical features encoded in the pharmacophore are in full agreement with the enzyme-inhibitor interaction pattern identified from molecular docking.
组蛋白脱乙酰酶（HDACs）通过修饰核小体的核心组蛋白在转录调控中发挥重要作用。它已成为治疗癌症和其他疾病的重要治疗靶点。HDACs抑制剂成为一类新型抗癌药物，并引起了药理学家和癌症研究人员的极大兴趣。为了促进特异性HDACs抑制剂的发现，开发了一种基于3D化学特征的QSAR药效团模型，该模型与HDAC抑制剂结合的结构功能要求高度一致。利用该模型，探索了苯甲酰胺MS-275与HDAC之间的相互作用。结果表明，药效团中编码的化学特征的类型和空间位置与从分子对接中确定的酶-抑制剂相互作用模式完全一致。
