5 alpha-reductase in intact DU145 cells: evidence for isozyme I and evaluation of novel inhibitors.
The epithelial-like human prostatic carcinoma cell line DU145, which expresses 5 alpha-reductase type I isozyme, was used to test a series of potential 5 alpha-reductase inhibitors. The exclusive expression of the type I isozyme was confirmed by PCR and subsequent DNA sequence analysis. Culture conditions were optimized for high conversion rates. Using this whole cell assay finasteride, 4MA, and 65 steroidal and non-steroidal compounds synthesized in our group were tested for their inhibitory activity. Inhibitors with IC50 values in the nanomolar range could be identified.
Reichert
W
W
Pharmaceutical and Medicinal Chemistry, Universität des Saarlandes, Saarbrücken, Germany.
Jose
J
J
Hartmann
R W
RW
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics / Q000378:metabolism; D058891:5-alpha Reductase Inhibitors; D004341:Drug Evaluation; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D015394:Molecular Structure; D017422:Sequence Analysis, DNA; D014407:Tumor Cells, Cultured / Q000201:enzymology
D058891:5-alpha Reductase Inhibitors; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase