title: Discovering potent small molecule inhibitors of cyclophilin A using de novo drug design approach.
abstract: This work describes an integrated approach of de novo drug design, chemical synthesis, and bioassay for quick identification of a series of novel small molecule cyclophilin A (CypA) inhibitors (1-3). The activities of the two most potent CypA inhibitors (3h and 3i) are 2.59 and 1.52 nM, respectively, which are about 16 and 27 times more potent than that of cyclosporin A. This study clearly demonstrates the power of our de novo drug design strategy and the related program LigBuilder 2.0 in drug discovery.
authors.affiliation: School of Pharmacy, East China University of Science and Technology, Shanghai, China.
authors.forename: Shuaishuai
authors.initials: S
authors.lastname: Ni
authors.forename: Yaxia
authors.initials: Y
authors.lastname: Yuan
authors.forename: Jin
authors.initials: J
authors.lastname: Huang
authors.forename: Xiaona
authors.initials: X
authors.lastname: Mao
authors.forename: Maosheng
authors.initials: M
authors.lastname: Lv
authors.forename: Jin
authors.initials: J
authors.lastname: Zhu
authors.forename: Xu
authors.initials: X
authors.lastname: Shen
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Pei
authors.forename: Luhua
authors.initials: L
authors.lastname: Lai
authors.forename: Hualiang
authors.initials: H
authors.lastname: Jiang
authors.forename: Jian
authors.initials: J
authors.lastname: Li
mesh_terms: D021984:Cyclophilin A / Q000037:antagonists & inhibitors* / Q000737:chemistry; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D011487:Protein Conformation; D012984:Software
chemical_list: D004791:Enzyme Inhibitors; D021984:Cyclophilin A