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.
Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
Ya-Dong
YD
Chen
Yong-Jun
YJ
Jiang
Jian-Wei
JW
Zhou
Qing-Sen
QS
Yu
Qi-Dong
QD
You
D000818:Animals; D001549:Benzamides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites; D020134:Catalytic Domain; D017076:Computer-Aided Design; D018360:Crystallography, X-Ray; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D021621:Imaging, Three-Dimensional; D007527:Isoenzymes / Q000737:chemistry; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D011487:Protein Conformation; D011725:Pyridines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D012984:Software
D001549:Benzamides; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D007527:Isoenzymes; D008024:Ligands; D011725:Pyridines; C118739:entinostat; D006655:Histone Deacetylases