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Integration of virtual screening with high-throughput screening for the identification of novel Rho-kinase I inhibitors

Paper ID Volume ID Publish Year Pages File Format Full-Text
24485 43518 2010 9 PDF Available
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 μmol l−1 and were worthy of further investigation.

Keywords
Virtual screening; High-throughput screening; Rho-kinase; Pharmacophore; LigandFit
First Page Preview
Integration of virtual screening with high-throughput screening for the identification of novel Rho-kinase I inhibitors
Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Biotechnology - Volume 145, Issue 3, 1 February 2010, Pages 295–303
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering