FCE 28260, a new 5 alpha-reductase inhibitor: in vitro and in vivo effects

J Steroid Biochem Mol Biol. 1996 Jun;58(3):299-305. doi: 10.1016/0960-0760(96)00040-4.

Abstract

FCE 28260 is a novel inhibitor of 5 alpha-reductase (5 alpha R), the enzyme responsible for the conversion of testosterone (T) to 5 alpha-dihydrotestosterone (DHT). The compound caused inhibition of rat and human prostatic enzymes, with IC50 values of 15 and 16 nM, respectively, compared to the values of 30 and 52 nM shown by finasteride. Furthermore, FCE 28260 was highly potent in inhibiting human recombinant 5 alpha 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 with an ED50 of 0.8 mg/kg, i.e. five times lower than that shown by finasteride. No anti-androgenic activity in DHT-implanted castrated rats was found up to 10 mg/kg/day. In adult male rats, FCE 28260 reduced prostatic DHT concentrations 6 h after oral dosing with a potency similar 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% reduction in prostate DHT at 10 mg/kg, compared to 26% reduction induced by finasteride). These results indicate that FCE 28260 represents a marked improvement over finasteride.

MeSH terms

  • 5-alpha Reductase Inhibitors*
  • Androstenes / metabolism
  • Androstenes / pharmacology*
  • Animals
  • Azasteroids / metabolism
  • Azasteroids / pharmacology*
  • Dihydrotestosterone / analysis
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Male
  • Prostate / enzymology*
  • Rats

Substances

  • (22RS-N-1,1,1-trifluoro-2-phenylprop-2-yl)-3-oxo-4-aza-5alpha-androst-1-ene-17beta-carboxamide
  • 5-alpha Reductase Inhibitors
  • Androstenes
  • Azasteroids
  • Enzyme Inhibitors
  • Dihydrotestosterone