Δ4-Abiraterone

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Δ4-Abiraterone
Clinical data
Synonyms D4A; CB-7627; 17-(3-Pyridyl)androsta-4,16-dien-3-one
Identifiers
CAS Number
PubChem CID
ChemSpider
Chemical and physical data
Formula C24H29NO
Molar mass 347.502 g/mol
3D model (JSmol)

Δ4-Abiraterone (D4A; code name CB-7627), also known as 17-(3-pyridyl)androsta-4,16-dien-3-one, is a steroidogenesis inhibitor and active metabolite of abiraterone acetate, a drug which is used in the treatment of prostate cancer and is itself a prodrug of abiraterone (another active metabolite of abiraterone acetate).[1] D4A is formed from abiraterone by 3β-hydroxysteroid dehydrogenase/Δ5-4 isomerase (3β-HSD).[1] It is said to be a more potent inhibitor of steroidogenesis than abiraterone, and is partially responsible for the activity of abiraterone acetate.[1]

D4A is specifically an inhibitor of CYP17A1 (17α-hydroxylase/17,20-lyase), 3β-HSD, and 5α-reductase;[1] in addition, it has also been found to act as a competitive antagonist of the androgen receptor (AR), with potency reportedly comparable to that of enzalutamide.[1] However, the initial 5α-reduced metabolite of D4A, 3-keto-5α-abiraterone, is an agonist of the AR, and has been found to stimulate prostate cancer progression.[2] The formation of this metabolite can be blocked by the coadministration of dutasteride, a selective and highly potent 5α-reductase inhibitor, and this addition may improve the effectiveness of abiraterone acetate in the treatment of prostate cancer.[2]

References[edit]

  1. ^ a b c d e 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. 
  2. ^ a b 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.