Journal article
Pharmacophore identification, docking and "in silico" screening for novel CDK1 inhibitors
ZJU-ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.1
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.
Language: | English |
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Year: | 2012 |
Pages: | 77-86 |
ISSN: | 18734243 and 10933263 |
Types: | Journal article |
DOI: | 10.1016/j.jmgm.2012.04.003 |