show add
hide add

Novel aromatase and 5 alpha-reductase inhibitors


Inhibitors of aromatase and 5 alpha-reductase may be of use for the therapy of postmenopausal breast cancer and benign prostatic hyperplasia, respectively. FCE 27993 is a novel steroidal irreversible aromatase inhibitor structurally related to exemestane (FCE 24304). The compound was found to be a very potent competitive inhibitor of human placental aromatase, with a Ki of 7.2 nM (4.3 nM for exemestane). In preincubation studies with placental aromatase FCE 27993, like exemestane, was found to cause time-dependent inhibition with a higher rate of inactivation (t1/2 4.5 vs 15.1 min) and a similar Ki(inact) (56 vs 66 nM). The compound was found to have a very low binding affinity to the androgen receptor (RBA 0.09% of dihydrotestosterone) and, in contrast to exemestane, no androgenic activity up to 100 mg/kg/day s.c. in immature castrated rats. Among a series of novel 4-azasteroids with fluoro-substituted-17 beta-amidic side chains, three compounds, namely FCE 28260, FCE 28175 and FCE 27837, were identified as potent in vitro and in vivo inhibitors of prostatic 5 alpha-reductase. Their IC50 values were found to be 16, 38 and 51 nM for the inhibition of the human enzyme, and 15, 20 and 60 nM for the inhibition of the rat enzyme, respectively. When given orally for 7 days in castrated and testosterone (Silastic implants) supplemented rats, the new compounds were very effective in reducing prostate growth. At a dose of 0.3 mg/kg/day inhibitions of 42, 36 and 41% were caused by FCE 28260, FCE 28175 and FCE 27837, respectively.



Di Salle E; Briatico G; Giudici D; Ornati G; Zaccheo T; Buzzetti F; Nesi M; Panzeri A



Pharmacia, R&D Oncology, Nerviano, Milano, Italy.



J Steroid Biochem Mol Biol, 1994 Jun, 49:4-6, 289-94





Unique Identifier:



    Shampoo for Women

    Blonde girl worried about hair loss

    ProTHIK Spray

    Tagamet (Cimetidine)

    Hair Loss Treatment

    man controls hair loss and unhappy gazing at you in the mirror 685775544 bald, baldness, loosing, prevention, hearttrob

    Male Pattern Alopecia

    Pin It on Pinterest

    Share This