Abiraterone

Abiraterone
Clinical data
Synonyms	CB-7598; 17-(3-Pyridyl)androsta-5,16-dien-3β-ol; Abiraterol
ATC code	L02BX03 (WHO) ;
Identifiers
	IUPAC name (3S,8R,9S,10R,13S,14S)-10,13-dimethyl-17-pyridin-3-yl-2,3,4,7,8,9,11,12,14,15-decahydro-1H-cyclopenta[a]phenanthren-3-ol;
CAS Number	154229-19-3 ;
PubChem CID	132971;
ChemSpider	117349 ;
UNII	G819A456D0;
PDB ligand	AER (PDBe, RCSB PDB);
Chemical and physical data
Formula	C24H31NO
Molar mass	349.52 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C[C@]12CC[C@@H](CC1=CC[C@@H]3[C@@H]2CC[C@]4([C@H]3CC=C4C5=CN=CC=C5)C)O;
	InChI InChI=1S/C24H31NO/c1-23-11-9-18(26)14-17(23)5-6-19-21-8-7-20(16-4-3-13-25-15-16)24(21,2)12-10-22(19)23/h3-5,7,13,15,18-19,21-22,26H,6,8-12,14H2,1-2H3/t18-,19-,21-,22-,23-,24+/m0/s1 ; Key:GZOSMCIZMLWJML-VJLLXTKPSA-N ;
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Abiraterone, developmental code name CB-7598, also known as 17-(3-pyridyl)androsta-5,16-dien-3β-ol, is a synthetic, steroidal CYP17A1 inhibitor. It is the active metabolite of abiraterone acetate, an ester and prodrug of abiraterone.

A metabolite of abiraterone has been found to act as an agonist of the androgen receptor, and may antagonize the clinical effectiveness of abiraterone acetate.^[1]

Abiraterone acetate

Abiraterone acetate (brand names Zytiga, Abiratas, Abretone, Abirapro) is used in the treatment of prostate cancer.^[2]^[3] Prostate cancer cells are stimulated to grow and spread by circulating androgen hormones. The intended effect of the drug is to block both physiologic and tumor-related androgen (e.g. testosterone) production, in order to slow or stop the spread of cancer cells.^[4] Since the drug blocks normal physiologic production of steroids by the adrenal glands, it is commonly prescribed with a low-dose steroid in order to prevent adrenal insufficiency.

In addition to acting as an irreversible inhibitor of CYP17A1 (17α-hydroxylase/17,20-lyase), abiraterone inhibits 3β-hydroxysteroid dehydrogenase (3β-HSD), steroid 11β-hydroxylase (CYP11B1), 5α-reductase (via a metabolite)^[5] and certain hepatic cytochrome P450 enzymes (e.g., CYP1A2, CYP2C9, and CYP3A4).^[6] The drug acts as a partial antagonist of the androgen receptor and as an agonist of the estrogen receptor.^[6]^[7]

References

Δ⁴-Abiraterone

References

↑ 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. PMC 5111629. PMID 27225130.
↑ Janos Fischer; Wayne E. Childers (4 November 2016). Successful Drug Discovery. Wiley. pp. 117–135. ISBN 978-3-527-80032-2.
↑ Stephen Neidle (30 September 2013). Cancer Drug Design and Discovery. Academic Press. pp. 331–337. ISBN 978-0-12-397228-6.
↑ Ang JE, Olmos D, de Bono JS (March 2009). "CYP17 blockade by abiraterone: further evidence for frequent continued hormone-dependence in castration-resistant prostate cancer". British Journal of Cancer. 100 (5): 671–5. doi:10.1038/sj.bjc.6604904. PMC 2653756. PMID 19223900.
↑ 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 4506215. PMID 26030522.
1 2 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.
↑ 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.

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[LiAlyamani2016-1] 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. PMC 5111629. PMID 27225130.

[FischerChilders2016-2] Janos Fischer; Wayne E. Childers (4 November 2016). Successful Drug Discovery. Wiley. pp. 117–135. ISBN 978-3-527-80032-2.

[Neidle2013-3] Stephen Neidle (30 September 2013). Cancer Drug Design and Discovery. Academic Press. pp. 331–337. ISBN 978-0-12-397228-6.

[4] Ang JE, Olmos D, de Bono JS (March 2009). "CYP17 blockade by abiraterone: further evidence for frequent continued hormone-dependence in castration-resistant prostate cancer". British Journal of Cancer. 100 (5): 671–5. doi:10.1038/sj.bjc.6604904. PMC 2653756. PMID 19223900.

[LiBishop2015-5] 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 4506215. PMID 26030522.

[pmid24276076-6] 1 2 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.

[pmid27083183-7] 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.