MedKoo product information:

 Abiraterone

Description of Abiraterone: Abiraterone is the active metabolite of abiraterone acetate, which is an orally active acetate ester of the steroidal compound abiraterone with antiandrogen activity. Abiraterone acetate was approved by the U.S. Food and Drug Administration (FDA) in April 2011. Abiraterone inhibits the enzymatic activity of steroid 17alpha-monooxygenase (17alpha-hydrolase/C17,20 lyase complex), a member of the cytochrome p450 family that catalyzes the 17alpha-hydroxylation of steroid intermediates involved in testosterone synthesis. Administration of this agent may suppress testosterone production by both the testes and the adrenals to castrate-range levels. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).

Abiraterone  is the active metabolite of abirateraone acetate (tradename Zytiga), which  is an approved drug used in castration-resistant prostate cancer (formerly hormone-resistant or hormone-refractory prostate cancer) (prostate cancer not responding to androgen deprivation or treatment with antiandrogens). After an expedited six-month review, abiraterone acetate was approved by the U.S. Food and Drug Administration (FDA) in April 2011. In Phase III trials, it extended median survival to 15.8 months versus 11.2 months placebo, and the trial was stopped because of the successful outcome. A course of treatment costs $40,000. (source: http://en.wikipedia.org/wiki/Abiraterone).

Pharmacokinetic data:  Protein binding: >99%; Metabolism: CYP3A4- and SULT2A1-mediated;
Half-life: 12 ± 5 hours; Excretion Fecal (88%), renal (5%). (source: http://en.wikipedia.org/wiki/Abiraterone).

History of abiraterone: This drug was initially discovered in the Cancer Research UK Centre for Cancer Therapeutics  at the Institute of Cancer Research in London. Rights for commercialization of the drug were assigned to BTG plc, a UK company that manages commercialization activity in pharmaceuticals. BTG then licensed the product to Cougar Biotechnology which began development of the commercial product. In 2009, Cougar was acquired by Johnson & Johnson which is currently conducting clinical trials on abiraterone. (source: http://en.wikipedia.org/wiki/Abiraterone).

 Mechanism of Action of abiraterone acetate :

Abiraterone acetate (ZYTIGA) is converted in vivo to abiraterone, an androgen biosynthesis inhibitor, that inhibits 17 α-hydroxylase/C17,20-lyase (CYP17). This enzyme is expressed in testicular, adrenal, and prostatic tumor tissues and is required for androgen biosynthesis. CYP17 catalyzes two sequential reactions: 1) the conversion of pregnenolone and progesterone to their 17α-hydroxy derivatives by 17α-hydroxylase activity and 2) the subsequent formation of dehydroepiandrosterone (DHEA) and androstenedione, respectively, by C17, 20 lyase activity. DHEA and androstenedione are androgens and are precursors of testosterone. Inhibition of CYP17 by abiraterone can also result in increased mineralocorticoid production by the adrenals. Androgen sensitive prostatic carcinoma responds to treatment that decreases androgen levels. Androgen deprivation therapies, such as treatment with GnRH agonists or orchiectomy, decrease androgen production in the testes but do not affect androgen production by the adrenals or in the tumor. ZYTIGA decreased serum testosterone and other androgens in patients in the placebo-controlled phase 3 clinical trial. It is not necessary to monitor the effect of ZYTIGA on serum testosterone levels. Changes in serum prostate specific antigen (PSA) levels may be observed but have not been shown to correlate with clinical benefit in individual patients. (source: http://www.rxlist.com/zytiga-drug.htm).

Chemical synthesis of abiraterone:

Abiraterone can be synthesized using compound 1 as a starting material, which synthetic route was outlined as the following:

Reference:

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