title: High-throughput screening of 11beta-hydroxysteroid dehydrogenase type 1 in scintillation proximity assay format.
abstract: 11beta-Hydroxysteroid dehydrogenase type-1 (11beta-HSD1) is a potential target for the treatment of diabetes, obesity, and hyperlipidemia. This enzyme is mainly responsible for reactivating glucocorticoid hormone inside cells such as adipose cells and liver cells by converting the inactive cortisone to active cortisol. Enzyme assays for 11beta-HSD1 involve either a thin-layer chromatography or high-performance liquid chromatography step to separate cortisol from the substrate cortisone. This additional step is labor intensive and increases the assay time, which limits assay throughput. A homogenous scintillation proximity assay-based method has been recently developed that enables high-throughput screening of 11beta-HSD1 inhibitors. We have applied this novel 11beta-HSD1 assay to screening a large-size compound collection and identified several structural classes of lead compounds that selectively inhibit the activity of 11beta-HSD1.
authors.affiliation: Department of Automated Biotechnology, Merck & Co., North Wales, PA, USA.
authors.forename: Kelli
authors.initials: K
authors.lastname: Solly
authors.forename: Steven S
authors.initials: SS
authors.lastname: Mundt
authors.forename: Hratch J
authors.initials: HJ
authors.lastname: Zokian
authors.forename: Gloria Juy-Fang
authors.initials: GJ
authors.lastname: Ding
authors.forename: Anne
authors.initials: A
authors.lastname: Hermanowski-Vosatka
authors.forename: Berta
authors.initials: B
authors.lastname: Strulovici
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal; D016466:CHO Cells; D020650:Combinatorial Chemistry Techniques; D006224:Cricetinae; D003412:Cricetulus; D004791:Enzyme Inhibitors / Q000032:analysis / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D008861:Microsomes / Q000201:enzymology; D012588:Scintillation Counting / Q000379:methods*; D014162:Transfection; D014316:Tritium
chemical_list: D000911:Antibodies, Monoclonal; D004791:Enzyme Inhibitors; D014316:Tritium; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D006854:Hydrocortisone