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Identification of chemically diverse, novel inhibitors of 17β-hydroxysteroid dehydrogenase type 3 and 5 by pharmacophore-based virtual screening.

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Schuster Daniela, Kowalik Dorota, Kirchmair Johannes, Laggner Christian, Markt Patrick, Aebischer-Gumy Christel, Ströhle Fabian, Möller Gabriele, Wolber Gerhard, Wilckens Thomas, Langer Thierry, Odermatt Alex, Adamski Jerzy,
Project The Regulation of Glucocorticoid and Mineralocorticoid Hormone Action by 11beta-Hydroxysteroid Dehydrogenases
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Original article (peer-reviewed)

Journal The Journal of steroid biochemistry and molecular biology
Volume (Issue) 125(1-2)
Page(s) 148 - 61
Title of proceedings The Journal of steroid biochemistry and molecular biology
DOI 10.1016/j.jsbmb.2011.01.016


17β-Hydroxysteroid dehydrogenase type 3 and 5 (17β-HSD3 and 17β-HSD5) catalyze testosterone biosynthesis and thereby constitute therapeutic targets for androgen-related diseases or endocrine-disrupting chemicals. As a fast and efficient tool to identify potential ligands for 17βHSD3/5, ligand- and structure-based pharmacophore models for both enzymes were developed. The models were evaluated first by in silico screening of commercial compound databases and further experimentally validated by enzymatic efficacy tests of selected virtual hits. Among the 35 tested compounds, 11 novel inhibitors with distinct chemical scaffolds, e.g. sulfonamides and triazoles, and with different selectivity properties were discovered. Thereby, we provide several potential starting points for further 17β-HSD3 and 17β-HSD5 inhibitor development. Article from the Special issue on Targeted Inhibitors.