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 IIclinical 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 dehydrogenasein 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 enzymeCYP3A4in vivo in rats.[10]
v
t
Relative potencies of selected antiandrogens
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 castratedimmature male rats. Sources: See template.
^ abcSchröder, Fritz H.; Radlmaier, Albert (2009). "Steroidal Antiandrogens". In V. Craig Jordan; Barrington J. A. Furr (eds.). Hormone Therapy in Breast and Prostate Cancer. Humana Press. pp. 325–346. doi:10.1007/978-1-59259-152-7_15. ISBN978-1-60761-471-5.
^ abAlan J. Wein; Louis R. Kavoussi; Andrew C. Novick; Alan W. Partin; Craig A. Peters (28 September 2011). Campbell-Walsh Urology. Elsevier Health Sciences. pp. 2637–. ISBN978-1-4557-2298-3.
^Winneker RC, Wagner MM, Batzold FH (December 1989). "Studies on the mechanism of action of Win 49596: a steroidal androgen receptor antagonist". J. Steroid Biochem. 33 (6): 1133–8. doi:10.1016/0022-4731(89)90420-2. PMID2615358.
^Berger, B; Naadimuthu, A; Boddy, A; Fisher, H; Mcconnell, J; Milam, D; Mobley, D; Rajfer, J (1995). "The Effect of Zanoterone, a Steroidal Androgen Receptor Antagonist, in Men with Benign Prostatic Hyperplasia". The Journal of Urology. 154 (3): 1060–1064. doi:10.1016/S0022-5347(01)66976-3. ISSN0022-5347.
^Roberts, Alan E.; Ritz, Martha A.; Hoekstra, Susan; Descotes, Gerard; Hincks, Jeffrey R. (1996). "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. doi:10.1002/(SICI)1522-7146(1996)11:3<101::AID-JBT1>3.0.CO;2-O. ISSN0887-2082. PMID9029268.