04-01-2016, 11:29 PM
A complete inhibition of 17α-hydroxylase/17,20-lyase (a key enzyme in the biosynthesis of androgens) can suppress androgens. A new class steroidal of CYP17 inhibitors are being presently used. They inhibit DHT @ nearly 90%, from what I've been able to see is also lowers estrogen by 13%......not worry though, I have an solution.
the evaluation of potent inhibitors of male rat 17alpha-hydroxylase/C17,20-lyase.
Duc I1, Bonnet P, Duranti V, Cardinali S, Rivière A, De Giovanni A, Shields-Botella J, Barcelo G, Adje N, Carniato D, Lafay J, Pascal JC, Delansorne R.
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Abstract
The C(17,20)-lyase is a key enzyme in the biosynthesis of androgens by both the testes and adrenals. A complete inhibition of this enzyme would provide an alternative means of androgen suppression for the treatment of prostatic cancers. In the present study, the inhibitory effects of new non-steroidal compounds were tested in vitro on rat C(17,20)-lyase versus abiraterone, a reference steroidal inhibitor. Their activities were also evaluated in vivo on plasma testosterone (T) and luteinizing hormone (LH) levels and on testes, adrenals, seminal vesicles (SV) and ventral prostate (VP) weights after 3 days of oral treatment to adult male rats (50mg/kg per day p.o.). Inhibition in the nanomolar range was obtained with TX 977, the lead racemate product in this series, and optimization is ongoing based on a slight dissociation observed between its two diastereoisomers, TX 1196-11 (S) and TX 1197-11 ®. These non-steroidal compounds (including YM 55208, a reference competitor) proved to be more active in vivo than abiraterone acetate in this model, but the observed impact on adrenal weight suggests that the specificity of lyase inhibition versus corticosteroid biosynthesis deserves further investigations with this new class of potentially useful agents for the treatment of androgen-dependent prostate cancer.p
the evaluation of potent inhibitors of male rat 17alpha-hydroxylase/C17,20-lyase.
Duc I1, Bonnet P, Duranti V, Cardinali S, Rivière A, De Giovanni A, Shields-Botella J, Barcelo G, Adje N, Carniato D, Lafay J, Pascal JC, Delansorne R.
Author information
Abstract
The C(17,20)-lyase is a key enzyme in the biosynthesis of androgens by both the testes and adrenals. A complete inhibition of this enzyme would provide an alternative means of androgen suppression for the treatment of prostatic cancers. In the present study, the inhibitory effects of new non-steroidal compounds were tested in vitro on rat C(17,20)-lyase versus abiraterone, a reference steroidal inhibitor. Their activities were also evaluated in vivo on plasma testosterone (T) and luteinizing hormone (LH) levels and on testes, adrenals, seminal vesicles (SV) and ventral prostate (VP) weights after 3 days of oral treatment to adult male rats (50mg/kg per day p.o.). Inhibition in the nanomolar range was obtained with TX 977, the lead racemate product in this series, and optimization is ongoing based on a slight dissociation observed between its two diastereoisomers, TX 1196-11 (S) and TX 1197-11 ®. These non-steroidal compounds (including YM 55208, a reference competitor) proved to be more active in vivo than abiraterone acetate in this model, but the observed impact on adrenal weight suggests that the specificity of lyase inhibition versus corticosteroid biosynthesis deserves further investigations with this new class of potentially useful agents for the treatment of androgen-dependent prostate cancer.p