Ho

17a-Hydroxypregnenolone

Abiraterone acetate

17a-Hydroxypregnenolone

Dehydroepiandrosterone Androstenedione

Corticosteroids

Androgens

FIGURE 3.23 Antiandrogens that interfere with the conversion of lanosterol into steroidal hormones.

CO-NH2

H3C OH

H3C OH

5a-Dihydrotestosterone

FIGURE 3.24 Reduction of testosterone to 5a-dihydrotestosterone.

Sa-Reductase -AyH Testosterone

5a-Dihydrotestosterone

FIGURE 3.24 Reduction of testosterone to 5a-dihydrotestosterone.

the prostate, without blocking peripheral androgenic action due to testosterone. Their main use so far is the treatment of alopecia and benign prostate hyperplasia, and there is interest in their potential use as cancer chemopreventive agents.

5a-Reductase is associated with the nuclear membrane and requires hydride donation from NADH, which acts as a cofactor and is transformed into NAD+ (Fig. 3.24).

Finasteride, the first inhibitor of this enzyme to reach the market, is believed to be a mechanism-based inhibitor acting through the mechanism shown in Fig. 3.25, which involves the addition of hydride to the unsaturated lactam system in

FIGURE 3.25 Inhibition of 5a-reductase by finasteride.

finasteride followed by trapping of the highly electrophilic NAD+ molecule by enol 3.29 generated in the first step.41

Dutasteride (GI-198745) is an analog of finasteride that behaves as a dual inhibitor of 5-a-reductase type 1 and 2 isozymes. This compound is approved for benign prostate hyperplasia and has been proposed for the chemoprevention of prostate cancer in men at high risk.42

10 Ways To Fight Off Cancer

10 Ways To Fight Off Cancer

Learning About 10 Ways Fight Off Cancer Can Have Amazing Benefits For Your Life The Best Tips On How To Keep This Killer At Bay Discovering that you or a loved one has cancer can be utterly terrifying. All the same, once you comprehend the causes of cancer and learn how to reverse those causes, you or your loved one may have more than a fighting chance of beating out cancer.

Get My Free Ebook


Post a comment