title: Hits identified in library screening demonstrate selective CYP17A1 lyase inhibition.
abstract: A screening of structurally different steroid hormone synthesis inhibitors was performed in order to find a starting point for the development of a new inhibitor of the bifunctional steroidogenic enzyme CYP17A1. Emphasis was placed on determination of selectivity between the two catalytic steps, namely 17α-hydroxylase and C(17,20)-lyase. For that purpose a new inhibition assay has been developed. Hits identified within this novel assay demonstrated selective inhibition of CYP17A1 lyase activity, and thus mark the basis for the development of selective C(17,20)-lyase inhibitors for the treatment of prostate cancer.
authors.affiliation: Pharmaceutical and Medicinal Chemistry, Saarland University, Campus C2.3, 66123 Saarbrücken, Germany.
authors.forename: Sebastian J
authors.initials: SJ
authors.lastname: Krug
authors.forename: Qingzhong
authors.initials: Q
authors.lastname: Hu
authors.forename: Rolf W
authors.initials: RW
authors.lastname: Hartmann
mesh_terms: D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000201:enzymology; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology*; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D054852:Small Molecule Libraries; C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase