Chemistry:Zanoterone
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| Other names | WIN-49596; (5α,17α)-1'-(methylsulfonyl)-1'-H-pregn-20-yno[3,2-c]pyrazol-17-ol |
| Routes of administration | By mouth |
| Drug class | Steroidal antiandrogen |
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| Formula | C23H32N2O3S |
| Molar mass | 416.58 g·mol−1 |
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Zanoterone (INN, USAN) (former developmental code name WIN-49596), also known as (5α,17α)-1'-(methylsulfonyl)-1'-H-pregn-20-yno[3,2-c]pyrazol-17-ol,[1] is a steroidal antiandrogen which was never marketed.[2][3][4] It was investigated for the treatment of benign prostatic hyperplasia (BPH) but failed to demonstrate sufficient efficacy in phase II clinical trials, and also showed an unacceptable incidence rate and severity of side effects (e.g., breast pain and gynecomastia).[4][5] As such, it was not further developed.[4][5]
Zanoterone was derived from 5α-dihydroethisterone (5α-dihydro-17α-ethynyltestosterone).[6][7] It is an antagonist of the androgen receptor (Ki = 2.2 μM; RBA compared to metribolone = 2.2%), and with the exception of antiprogestogenic activity in rat and rabbit models, is devoid of other hormonal activities.[6][8] Zanoterone does not inhibit 5α-reductase, aromatase, or 3α- or 3β-hydroxysteroid dehydrogenase in vitro.[6] The drug significantly increases testosterone and estradiol levels in men.[9] 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.[6] It has been found to act as an inducer of the enzyme CYP3A4 in vivo in rats.[10]
| Antiandrogen | Relative potency |
|---|---|
| Bicalutamide | 4.3 |
| Hydroxyflutamide | 3.5 |
| Flutamide | 3.3 |
| Cyproterone acetate | 1.0 |
| Zanoterone | 0.4 |
| Description: Relative potencies of orally administered antiandrogens in antagonizing 0.8 to 1.0 mg/kg s.c. testosterone propionate-induced ventral prostate weight increase in castrated immature male rats. Sources: See template. | |
See also
References
- ↑ William Andrew Publishing (22 October 2013). Pharmaceutical Manufacturing Encyclopedia, 3rd Edition. Elsevier. pp. 3517–3518. ISBN 978-0-8155-1856-3. https://books.google.com/books?id=_J2ti4EkYpkC&pg=PA3517.
- ↑ Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. 31 October 1999. pp. 294–. ISBN 978-0-7514-0499-9. https://books.google.com/books?id=mqaOMOtk61IC&pg=PA294.
- ↑ Dictionary of Pharmacological Agents. Taylor & Francis. 1997. pp. 540–. ISBN 978-0-412-46630-4. https://books.google.com/books?id=OlP5DIq1xZkC&pg=PA540.
- ↑ 4.0 4.1 4.2 "Steroidal Antiandrogens". Hormone Therapy in Breast and Prostate Cancer. Cancer Drug Discovery and Development. Humana Press. 2009. pp. 325–346. doi:10.1007/978-1-59259-152-7_15. ISBN 978-1-60761-471-5.
- ↑ 5.0 5.1 Campbell-Walsh Urology. Elsevier Health Sciences. 28 September 2011. pp. 2637–. ISBN 978-1-4557-2298-3. https://books.google.com/books?id=W1aeyJD46kIC&pg=PA2637.
- ↑ 6.0 6.1 6.2 6.3 "New horizons in the treatment of proliferative prostatic disease.". Annual Reports in Medicinal Chemistry. Academic Press. 8 September 1989. pp. 197-206 (200). ISBN 978-0-08-058368-6. https://books.google.com/books?id=HrALiG-4t7UC&pg=PA200.
- ↑ The Organic Chemistry of Drug Synthesis. John Wiley & Sons. 5 November 1998. p. 65. ISBN 978-0-471-24510-0. https://books.google.com/books?id=howvAQAAIAAJ.
- ↑ "Studies on the mechanism of action of Win 49596: a steroidal androgen receptor antagonist". Journal of Steroid Biochemistry 33 (6): 1133–1138. December 1989. doi:10.1016/0022-4731(89)90420-2. PMID 2615358.
- ↑ "The effect of zanoterone, a steroidal androgen receptor antagonist, in men with benign prostatic hyperplasia. The Zanoterone Study Group". The Journal of Urology 154 (3): 1060–1064. September 1995. doi:10.1016/S0022-5347(01)66976-3. PMID 7543598.
- ↑ "Induction of liver cytochrome P-450 (CYP) 3A in male and female rats by a steroidal androgen receptor antagonist, zanoterone". Journal of Biochemical Toxicology 11 (3): 101–110. 1996. doi:10.1002/(SICI)1522-7146(1996)11:3<101::AID-JBT1>3.0.CO;2-O. PMID 9029268.
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