title: Development of a biological screening system for the evaluation of highly active and selective 17beta-HSD1-inhibitors as potential therapeutic agents.
abstract: 17beta-Hydroxysteroid dehydrogenase type 1 (17beta-HSD1) catalyses the intracellular conversion of oestrone (E1) to oestradiol (E2). E2 is known to be involved in the development and progression of breast cancer and endometriosis. Since 17beta-HSD1 is overexpressed in these oestrogen-dependent diseases, inhibition of this enzyme may be a more target-directed therapeutical approach compared to established medical treatments. For the identification of highly active and selective 17beta-HSD1-inhibitors that are suitable for application as potential therapeutics, there is a need for an appropriate, efficient and reliable screening system. Here, we report the development and application of our screening system using our in house library of potential 17beta-HSD1-inhibitors. Four potent and selective compounds with a good first pharmacokinetic profile were identified.
authors.affiliation: 8.2 Pharmaceutical and Medicinal Chemistry, Saarland University, PO Box 15 11 50, D-66041 Saarbrücken, Germany.
authors.forename: Patricia
authors.initials: P
authors.lastname: Kruchten
authors.forename: Ruth
authors.initials: R
authors.lastname: Werth
authors.forename: Sandrine
authors.initials: S
authors.lastname: Marchais-Oberwinkler
authors.forename: Martin
authors.initials: M
authors.lastname: Frotscher
authors.forename: Rolf W
authors.initials: RW
authors.lastname: Hartmann
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D000818:Animals; D045744:Cell Line, Tumor; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D004958:Estradiol / Q000737:chemistry / Q000378:metabolism; D004970:Estrone / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004791:Enzyme Inhibitors; D004970:Estrone; D004958:Estradiol; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase