Structure-based virtual screening for identification of novel 11beta-HSD1 inhibitors.
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.
Yang
Huaiyu
H
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.
Shen
Yu
Y
Chen
Junhua
J
Jiang
Qunfeng
Q
Leng
Ying
Y
Shen
Jianhua
J
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors*; D000818:Animals; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure
D004791:Enzyme Inhibitors; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1