Zanoterone (, ) (former developmental code name WIN-49596), also known as (5α,17α)-1'-(methylsulfonyl)-1'-H-pregn-20-yno ,2-cyrazol-17-ol, is a steroidal antiandrogen which was never marketed. It was investigated for the treatment of

benign prostatic hyperplasia Benign prostatic hyperplasia (BPH), also called prostate enlargement, is a noncancerous increase in size of the prostate gland. Symptoms may include frequent urination, trouble starting to urinate, weak stream, inability to urinate, or loss o ...

(BPH) but failed to demonstrate sufficient efficacy in phase II

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, diet ...

s, and also showed an unacceptable incidence rate and severity of

side effect In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...

s (e.g., breast pain and

gynecomastia Gynecomastia (also spelled gynaecomastia) is the abnormal non-cancerous enlargement of one or both breasts in males due to the growth of breast tissue as a result of a hormone imbalance between estrogens and androgens. Updated by Brent Wisse ( ...

). As such, it was not further developed. Zanoterone was derived from 5α-dihydroethisterone (5α-dihydro-17α-ethynyltestosterone). It is an antagonist of the androgen receptor (K_i = 2.2 μM; compared to

metribolone Metribolone (developmental code R1881, also known as methyltrienolone) is a synthetic and orally active anabolic–androgenic steroid (AAS) and a 17α-alkylated nandrolone (19-nortestosterone) derivative which was never marketed for medical ...

= 2.2%), and with the exception of

antiprogestogen Antiprogestogens, or antiprogestins, also known as progesterone antagonists or progesterone blockers, are a class of drugs which prevent progestogens like progesterone from mediating their biological effects in the body. They act by blocking the ...

ic activity in rat and rabbit models, is devoid of other hormonal activities. Zanoterone does not inhibit 5α-reductase,

aromatase Aromatase (), also called estrogen synthetase or estrogen synthase, is an enzyme responsible for a key step in the biosynthesis of estrogens. It is CYP19A1, a member of the cytochrome P450 superfamily, which are monooxygenases that catalyze many ...

, or 3α- or 3β-hydroxysteroid dehydrogenase ''

in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology ...

''. The drug significantly increases

testosterone Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of male reproductive tissues such as testes and prostate, as well as promoting secondary sexual characteristi ...

and

estradiol Estradiol (E2), also spelled oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of the estrous and menstrual female reproductive cycles. Estradiol is responsible for the development o ...

levels in men. Zanoterone has been found to not significantly inhibit mating performance or fertility in adult male rats at high dosages for an extended period of time. It has been found to act as an

inducer In molecular biology, an inducer is a molecule that regulates gene expression. An inducer functions in two ways; namely: *By disabling repressors. The gene is expressed because an inducer binds to the repressor. The binding of the inducer to the r ...

of the

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...

CYP3A4 ''

in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...

'' in rats.

References

Abandoned drugs Androstanes Antiprogestogens Progonadotropins Pyrazoles Steroidal antiandrogens Sulfonamides {{Antineoplastic-drug-stub

See also

References