title: Discovery of novel human acrosin inhibitors by virtual screening.
abstract: Human acrosin is an attractive target for the discovery of male contraceptive drugs. For the first time, structure-based drug design was applied to discover structurally diverse human acrosin inhibitors. A parallel virtual screening strategy in combination with pharmacophore-based and docking-based techniques was used to screen the SPECS database. From 16 compounds selected by virtual screening, a total of 10 compounds were found to be human acrosin inhibitors. Compound 2 was found to be the most potent hit (IC(50) = 14 μM) and its binding mode was investigated by molecular dynamics simulations. The hit interacted with human acrosin mainly through hydrophobic and hydrogen-bonding interactions, which provided a good starting structure for further optimization studies.
authors: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
authors: Xuefei
authors: X
authors: Liu
authors: Guoqiang
authors: G
authors: Dong
authors: Jue
authors: J
authors: Zhang
authors: Jingjing
authors: J
authors: Qi
authors: Canhui
authors: C
authors: Zheng
authors: Youjun
authors: Y
authors: Zhou
authors: Ju
authors: J
authors: Zhu
authors: Chunquan
authors: C
authors: Sheng
authors: Jiaguo
authors: J
authors: Lü
mesh_terms: D000176:Acrosin / Q000037:antagonists & inhibitors* / Q000737:chemistry; D020134:Catalytic Domain; D003272:Contraceptive Agents, Male / Q000737:chemistry* / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D008297:Male; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D015842:Serine Proteinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D003272:Contraceptive Agents, Male; D015842:Serine Proteinase Inhibitors; D000176:Acrosin