Discovery of novel inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 by docking and pharmacophore modeling

Huaiyu Yang; Wei Dou; Jing Lou; Ying Leng; Jianhua Shen

doi:10.1016/j.bmcl.2008.01.020

Discovery of novel inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 by docking and pharmacophore modeling

Bioorg Med Chem Lett. 2008 Feb 15;18(4):1340-5. doi: 10.1016/j.bmcl.2008.01.020. Epub 2008 Jan 11.

Authors

Huaiyu Yang¹, Wei Dou, Jing Lou, 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, China.

PMID: 18242087
DOI: 10.1016/j.bmcl.2008.01.020

Abstract

11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) is a potential target for treatment of diabetes and metabolic syndrome. Docking and pharmacophore modeling have been used to discover novel inhibitors of 11beta-HSD1. Several compounds, with large structural diversity and good potency against 11beta-HSD1, have been found and their potency was determined by the enzyme assay. New scaffolds of 11beta-HSD1 inhibitors are also reported.

Publication types

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

MeSH terms

11-beta-Hydroxysteroid Dehydrogenase Type 1 / antagonists & inhibitors*
11-beta-Hydroxysteroid Dehydrogenase Type 1 / chemistry
11-beta-Hydroxysteroid Dehydrogenase Type 2 / antagonists & inhibitors
Animals
Crystallography, X-Ray
Drug Design
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacology*
Humans
Hydrogen Bonding
Inhibitory Concentration 50
Mice
Models, Molecular
Structure-Activity Relationship

Substances

Enzyme Inhibitors
11-beta-Hydroxysteroid Dehydrogenase Type 1
11-beta-Hydroxysteroid Dehydrogenase Type 2