Structure-based virtual screening for identification of novel 11beta-HSD1 inhibitors

Huaiyu Yang; Yu Shen; Junhua Chen; Qunfeng Jiang; Ying Leng; Jianhua Shen

doi:10.1016/j.ejmech.2008.06.005

Structure-based virtual screening for identification of novel 11beta-HSD1 inhibitors

Eur J Med Chem. 2009 Mar;44(3):1167-71. doi: 10.1016/j.ejmech.2008.06.005. Epub 2008 Jun 20.

Authors

Huaiyu Yang¹, Yu Shen, Junhua Chen, Qunfeng Jiang, Ying Leng, Jianhua Shen

Affiliation

¹ Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Science and the Graduate School, Chinese Academy of Sciences, 555 Zuchongzhi Road, 201203 Shanghai, China.

PMID: 18653260
DOI: 10.1016/j.ejmech.2008.06.005

Abstract

Structure-based pharmacophore models were built by using LigandScout and used for virtual screening of the SPECS database to identify new potential 11beta-HSD1 inhibitors. As a refinement of the results obtained from virtual 3D pharmacophore screening, the best fitting virtual hits were subjected to docking study. The resulting compounds were tested in an enzyme assay and revealed several compounds with novel scaffolds that show sub-micromolar activity and high selectivity for 11beta-HSD1 against 11beta-HSD2.

Publication types

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

MeSH terms

11-beta-Hydroxysteroid Dehydrogenase Type 1 / antagonists & inhibitors*
Animals
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacology
Humans
Mice
Models, Molecular
Molecular Structure

Substances

Enzyme Inhibitors
11-beta-Hydroxysteroid Dehydrogenase Type 1