Pharmacophore-based virtual screening: the discovery of novel methionyl-tRNA synthetase inhibitors

Su Yeon Kim; Yeon-Sook Lee; Taehee Kang; Sunghoon Kim; Jeewoo Lee

doi:10.1016/j.bmcl.2006.06.057

Pharmacophore-based virtual screening: the discovery of novel methionyl-tRNA synthetase inhibitors

Bioorg Med Chem Lett. 2006 Sep 15;16(18):4898-907. doi: 10.1016/j.bmcl.2006.06.057. Epub 2006 Jul 7.

Authors

Su Yeon Kim¹, Yeon-Sook Lee, Taehee Kang, Sunghoon Kim, Jeewoo Lee

Affiliation

¹ Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shinlim-Dong, Kwanak-Ku, Seoul 151-742, Republic of Korea.

PMID: 16824759
DOI: 10.1016/j.bmcl.2006.06.057

Abstract

We have performed virtual screening of a chemical database of 508,143 commercially available chemicals to search for new methionyl-tRNA synthetase (MetRS) inhibitors. In this study, potent lead compounds with a novel skeleton, including compound 27 with IC50 = 237 nM, were successfully identified as Escherichia coli MetRS inhibitors.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Binding Sites
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacology*
Escherichia coli / enzymology
Methionine-tRNA Ligase / antagonists & inhibitors*
Methionine-tRNA Ligase / chemistry
Methionine-tRNA Ligase / metabolism*
Models, Molecular
Molecular Structure
Structure-Activity Relationship

Substances

Enzyme Inhibitors
Methionine-tRNA Ligase