Zanoterone

From Wikipedia, the free encyclopedia
Jump to navigation Jump to search
Zanoterone
Zanoterone.svg
Clinical data
Synonyms 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
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
Chemical and physical data
Formula C23H32N2O3S
Molar mass 416.577 g/mol
3D model (JSmol)

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).[5][6] As such, it was not further developed.[5][6]

Zanoterone was derived from 5α-dihydroethisterone (5α-dihydro-17α-ethynyltestosterone).[7][8] It is an antagonist of the androgen receptor (Ki = 2.2 μM), and with the exception of antiprogestogenic activity in rat and rabbit models, is devoid of other hormonal activities.[7] Zanoterone does not inhibit 5α-reductase, aromatase, or 3α- or 3β-hydroxysteroid dehydrogenase in vitro.[7] 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.[7] It has been found to act as an inducer of the enzyme CYP3A4 in vivo in rats.[10]

See also[edit]

References[edit]

  1. ^ William Andrew Publishing (22 October 2013). Pharmaceutical Manufacturing Encyclopedia, 3rd Edition. Elsevier. pp. 3517–3518. ISBN 978-0-8155-1856-3. 
  2. ^ Dr. Ian Morton; I.K. Morton; Judith M. Hall (31 October 1999). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 294–. ISBN 978-0-7514-0499-9. 
  3. ^ C.R. Ganellin; David J. Triggle (1997). Dictionary of Pharmacological Agents. Taylor & Francis. pp. 540–. ISBN 978-0-412-46630-4. 
  4. ^ JORDAN V. CRAIG; B.J.A. Furr (5 February 2010). Hormone Therapy in Breast and Prostate Cancer. Springer Science & Business Media. pp. 328–. ISBN 978-1-59259-152-7. 
  5. ^ a b Virgil Craig Jordan; B. J. A. Furr (5 February 2010). Hormone Therapy in Breast and Prostate Cancer. Springer Science & Business Media. pp. 328–. ISBN 978-1-59259-152-7. 
  6. ^ a b Alan 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–. ISBN 1-4557-2298-7. 
  7. ^ a b c d Annual Reports in Medicinal Chemistry. Academic Press. 8 September 1989. pp. 200–. ISBN 978-0-08-058368-6. 
  8. ^ Daniel Lednicer; Lester A. Mitscher (5 November 1998). The Organic Chemistry of Drug Synthesis. John Wiley & Sons. p. 65. ISBN 978-0-471-24510-0. 
  9. ^ 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. ISSN 0022-5347. 
  10. ^ 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. ISSN 0887-2082. PMID 9029268.