Identification of ligand features essential for HDACs inhibitors by pharmacophore modeling
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.
Keywords: Histone deacetylases enzyme Inhibitor Pharmacophore model FlezX Docking
Ya-dong Chen Yong-Jun Jiang Jian-Wei Zhou Qing-Sen Yu Qi-Dong You
Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, Ningbo Institute of Technology, Zhejiang University, Ningbo 315104, PR China
国际会议
广州
英文
266-274
2008-11-01（万方平台首次上网日期，不代表论文的发表时间）