FCE-28260, A NEW 5-ALPHA-REDUCTASE INHIBITOR - IN-VITRO AND IN-VIVO EFFECTS

FCE 28260 is a novel inhibitor of 5 alpha-reductase (5 alpha R), the e nzyme responsible for the conversion of testosterone (T) to 5 alpha-di hydrotestosterone (DHT). The compound caused inhibition of rat and hum an prostatic enzymes, with IC50 values of 15 and 16 nM, respectively, compared to the values of 30 and 52 nM< shown by finasteride. Furtherm ore, FCE 28260 was highly potent in inhibiting human recombinant 5 alp ha R type 2 and 1 isozymes, showing IC50 values of 3.3 and 36 nM, and therefore it was more potent than finasteride (IC50 values of 8.5 and 470 nM) on both isozymes. In prepubertal, T-implanted castrated rats, FCE 28260, given orally for 7 days, reduced ventral prostate growth wi th an ED(50) of 0.8 mg/kg, i.e. five times lower than that shown by fi nasteride. No anti-androgenic activity in DHT-implanted castrated rats was found up to 10 mg/kg/day. In adult male rats, FCE 28260 reduced p rostatic DHT concentrations 6 h after oral dosing with a potency simil ar to that of finasteride (65% reduction at 1 mg/kg) but was found to be markedly more potent than the reference compound at 24 h (74% reduc tion in prostate DHT at 10 mg/kg, compared to 26% reduction induced by finasteride). These results indicate that FCE 28260 represents a mark ed improvement over finasteride. Copyright (C) 1996 Elsevier Science L imited.