Abiraterone

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Abiraterone
Abiraterone.svg
Abiraterone3Dan.gif
Identifiers
Synonyms CB-7598; 17-(3-pyridyl)androsta-5,16-dien-3β-ol
CAS Number 154229-19-3
PubChem (CID) 132971
ChemSpider 117349
UNII G819A456D0
Chemical and physical data
Formula C24H31NO
Molar mass 349.52 g·mol−1
3D model (Jmol) Interactive image

Abiraterone (INN, BAN) (developmental code name CB-7598), also known as 17-(3-pyridyl)androsta-5,16-dien-3β-ol, is a synthetic, steroidal CYP17A1 inhibitor and the active metabolite of abiraterone acetate, an ester and prodrug of abiraterone that is used in the treatment of prostate cancer.[1][2] In addition to acting as an irreversible inhibitor of CYP17A1 (17α-hydroxylase/17,20-lyase), abiraterone has also been found to inhibit 3β-hydroxysteroid dehydrogenase (3β-HSD), steroid 11β-hydroxylase (CYP11B1), 5α-reductase (via a metabolite),[3] and certain hepatic cytochrome P450 enzymes (e.g., CYP1A2, CYP2C9, and CYP3A4).[4] The drug has been found to act as a partial antagonist of the androgen receptor and as an agonist of the estrogen receptor as well,[4][5] and a metabolite of abiraterone has been found to act as an agonist of the androgen receptor.[6]

Clinically, it is used in the form of abiraterone acetate (trade name Zytiga, among others).

References[edit]

  1. ^ Janos Fischer; Wayne E. Childers (4 November 2016). Successful Drug Discovery. Wiley. pp. 117–135. ISBN 978-3-527-80032-2. 
  2. ^ Stephen Neidle (30 September 2013). Cancer Drug Design and Discovery. Academic Press. pp. 331–337. ISBN 978-0-12-397228-6. 
  3. ^ Li Z, Bishop AC, Alyamani M, Garcia JA, Dreicer R, Bunch D, Liu J, Upadhyay SK, Auchus RJ, Sharifi N (July 2015). "Conversion of abiraterone to D4A drives anti-tumour activity in prostate cancer". Nature. 523 (7560): 347–51. doi:10.1038/nature14406. PMC 4506215Freely accessible. PMID 26030522. 
  4. ^ a b Yin L, Hu Q (January 2014). "CYP17 inhibitors--abiraterone, C17,20-lyase inhibitors and multi-targeting agents". Nature Reviews. Urology. 11 (1): 32–42. doi:10.1038/nrurol.2013.274. PMID 24276076. 
  5. ^ Capper CP, Larios JM, Sikora MJ, Johnson MD, Rae JM (May 2016). "The CYP17A1 inhibitor abiraterone exhibits estrogen receptor agonist activity in breast cancer". Breast Cancer Research and Treatment. 157 (1): 23–30. doi:10.1007/s10549-016-3774-3. PMID 27083183. 
  6. ^ Li Z, Alyamani M, Li J, Rogacki K, Abazeed M, Upadhyay SK, Balk SP, Taplin ME, Auchus RJ, Sharifi N (May 2016). "Redirecting abiraterone metabolism to fine-tune prostate cancer anti-androgen therapy". Nature. 533 (7604): 547–51. doi:10.1038/nature17954. PMID 27225130.