title: Pharmacophore identification, docking and "in silico" screening for novel CDK1 inhibitors.
abstract: Pharmacophore models of cyclin-dependent kinase-1 (CDK1) inhibitors were established by using the Catalyst/HypoGen. The best pharmacophore model, Hypo1, consists of one hydrogen bond acceptor (HBA), one hydrogen bond donor (HBD), one hydrophobic (HY) and one ring aromatic (RA) feature. The validation results of Hypo1 through cost analysis, test set prediction, Fisher's cross method and receiver operating characteristic (ROC) study indicated that the Hypo1 was statistically valuable and reliable in identifying structural diverse CDK1 inhibitors. It is further supported by the consistent results from molecular docking studies. Finally, the Hypo1 was used to "in silico" screen the NCI and MayBridge database. The preferable hits obtained were further docked into ATP binding site of CDK1, and nine promising compounds were retrieved as novel potential CDK1 inhibitors for further studies.
authors.affiliation: ZJU-ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Xiaowu
authors.initials: X
authors.lastname: Dong
authors.forename: Jingying
authors.initials: J
authors.lastname: Yan
authors.forename: Lilin
authors.initials: L
authors.lastname: Du
authors.forename: Peng
authors.initials: P
authors.lastname: Wu
authors.forename: Shufang
authors.initials: S
authors.lastname: Huang
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Yongzhou
authors.initials: Y
authors.lastname: Hu
mesh_terms: D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors*; D030541:Databases, Genetic; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006860:Hydrogen Bonding; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D016203:CDC2 Protein Kinase