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Hair Loss Study Abstract: FK143, a novel nonsteroidal inhibitor of steroid 5 alpha-reductase: (1) In vitro
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Title
FK143, a novel nonsteroidal inhibitor of steroid 5 alpha-reductase: (1) In vitro effects
on human and animal prostatic enzymes.
Author
Hirosumi J; Nakayama O; Fagan T; Sawada K; Chida N; Inami M; Takahashi S; Kojo H; Notsu
Y; Okuhara M
Address
Exploratory Research Laboratories, Fujisawa Pharmaceutical Co. Ltd, Tsukuba Japan.
Source
J Steroid Biochem Mol Biol, 1995 Apr, 52:4, 357-63
Abstract
Steroid 5 alpha-reductase is an enzyme which converts testosterone into 5
alpha-dihydrotestosterone (DHT) and is implicated in the pathogenesis of benign prostatic
hyperplasia (BPH) in men. We studied in vitro effects of FK143, a nonsteroidal new
compound, on 5 alpha-reductase in human and animal prostates. Prostates were obtained from
Wistar rats, Beagle dogs, and Cynomolgus monkeys as well as prostatic tissue from BPH
patients obtained by the prostatectomy. Nuclear membrane fraction of prostates showed pH
dependent 5 alpha-reductase activities, and inhibitory effects of drugs were assayed at pH
6.5. FK143 inhibited human prostatic 5 alpha-reductase in a dose-dependent manner with an
IC50 of 1.9 nM and also inhibited animal 5 alpha-reductases with similar IC50 values.
FK143 inhibited human and rat 5 alpha-reductases in a noncompetitive fashion while
finasteride, a steroidal 5 alpha-reductase inhibitor, showed competitive inhibition. The
affinities of FK143 for the human 5 alpha-reductase is constant at pH 5 and 6.5. No
inhibitory effects were shown to other oxidoreductases. These results indicate that FK143
is a new type of potent and selective 5 alpha-reductase inhibitor.
Language of Publication
LA=ENG
Unique Identifier
95252171
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