Chemistry:Δ4-Abiraterone
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| Other names | D4A; CB-7627; 17-(3-Pyridyl)androsta-4,16-dien-3-one |
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| Formula | C24H29NO |
| Molar mass | 347.502 g·mol−1 |
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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 the addition of this medication may improve the effectiveness of abiraterone acetate in the treatment of prostate cancer.[2]
References
- ↑ 1.0 1.1 1.2 1.3 1.4 "Conversion of abiraterone to D4A drives anti-tumour activity in prostate cancer". Nature 523 (7560): 347–51. July 2015. doi:10.1038/nature14406. PMID 26030522. Bibcode: 2015Natur.523..347L.
- ↑ 2.0 2.1 "Redirecting abiraterone metabolism to fine-tune prostate cancer anti-androgen therapy". Nature 533 (7604): 547–51. May 2016. doi:10.1038/nature17954. PMID 27225130. PMC 5111629. Bibcode: 2016Natur.533..547L. https://dash.harvard.edu/bitstream/handle/1/29626087/5111629.pdf?sequence=1.
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