J. Hirosumi et al., FK143, A NOVEL NONSTEROIDAL INHIBITOR OF STEROID 5-REDUCTASE .1. IN-VITRO EFFECTS ON HUMAN AND ANIMAL PROSTATIC ENZYMES, Journal of steroid biochemistry and molecular biology, 52(4), 1995, pp. 357-363
Steroid 5 alpha-reductase is an enzyme which converts testosterone int
o 5 alpha-dihydrotestosterone (DHT) and is implicated in the pathogene
sis 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 inh
ibitory effects of drugs were assayed at pH 6.5. FK143 inhibited human
prostatic 5 alpha-reductase in a dose-dependent manner with an IC50 o
f 1.9nM and also inhibited animal 5 alpha-reductases with similar IC50
values. FK143 inhibited human and rat 5 alpha-reductases in a noncomp
etitive fashion while finasteride, a steroidal 5 alpha-reductase inhib
itor, showed competitive inhibition. The affinities of FK143 for the h
uman 5 alpha-reductase is constant at pH5 and 6.5. No inhibitory effec
ts were shown to other oxidoreductases. These results indicate that FK
143 is a new type of potent and selective 5 alpha-reductase inhibitor.