title: Integration of virtual screening with high-throughput screening for the identification of novel Rho-kinase I inhibitors.
abstract: Rho-kinase inhibitors are effective candidates for the treatment of neural and cardiovascular disorders. The present paper reports the discovery of a novel class of ROCK-I inhibitors by integrating virtual screening with high-throughput screening methods. We developed common-feature pharmacophore models based on known representative ROCK inhibitors and employed them to screen a database of 12,280 compounds. We then applied a LigandFit model to reduce the number of hits. A new high-throughput screening model based on Kinase-Glo Luminescent Kinase Assay was established to identify inhibitors observed among the virtual screening models. Ten hits were found to have larger than 70% inhibition at 10 micromol l(-1) and were worthy of further investigation.
authors: Institute of Materia Medica, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China.
authors: Li-Li
authors: LL
authors: Gong
authors: Lian-Hua
authors: LH
authors: Fang
authors: Jian-Hao
authors: JH
authors: Peng
authors: Ai-Lin
authors: AL
authors: Liu
authors: Guan-Hua
authors: GH
authors: Du
mesh_terms: D004591:Electrophoresis, Polyacrylamide Gel; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000032:analysis* / Q000737:chemistry / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000378:metabolism; D014584:User-Computer Interface; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors* / Q000302:isolation & purification / Q000378:metabolism
chemical_list: D047428:Protein Kinase Inhibitors; D011994:Recombinant Proteins; D054460:rho-Associated Kinases