Abiraterone  (Synonyms: CB-7598)

Abiraterone is a potent and irreversible CYP17A1 inhibitor with antiandrogen activity, which inhibits both the 17α-hydroxylase and 17,20-lyase activity of the cytochrome p450 enzyme CYP17 with IC₅₀s of 2.5 nM and 15 nM, respectively.

Significant inhibition of proliferation of the AR-positive prostate cancer cell lines LNCaP and VCaP with doses of Abiraterone ≥5 μM is confirmed^[2]. Abiraterone shows IC₅₀ values of 15 nM and 2.5 nM for the 17,20-lyase and 17α-hydroxylase (CYP17 is a bifunctional enzyme with both 17α-hydroxylase and 17,20-lyase activity). Abiraterone inhibits human 17,20-lyase and 17α-hydroxylase with IC₅₀ of 27 and 30 nM respectively^[3]. Abiraterone inhibits recombinant human 3βHSD1 and 3βHSD2 activity with competitive K_i values of 2.1 and 8.8 μM. 10 μM Abiraterone is sufficient to completely block synthesis of 5α-dione and DHT in both cell lines.Treatment with abi significantly inhibited CRPC progression in the robustly growing subset, effectively putting a ceiling on tumor growth over 4 weeks of treatment (P<0.00001). [³H]-dehydroepiandrosterone (DHEA) depletion and Δ⁴-androstenedione (AD) accumulation are inhibited by Abiraterone in LNCaP, with an IC₅₀<1 μM^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

The 0.5 mmol/kg/d Abiraterone treatment dose is previously shown to yield serum concentrations of about 0.5 to 1 μM. Xenograft tumor growth in the control group is widely variable, with some tumors growing slowly and only a subset of tumors exhibiting robust growth^[4]. Following i.v. administration (5 mg/kg) the clearance (Cl) and volume of distribution (V_d) are found to be 31.2 mL/min/kg and 1.97 L/kg, respectively. The AUC_0-∞ (area under the plasma concentration-time curve from time zero to infinity time point) is found to be 2675 ng*h/mL. The terminal half-life (t_1/2) is 0.73 h. Because of high clearance, Abiraterone (ART) is quantifiable only until 2 h following i.v. administration^[5].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

349.51

C₂₄H₃₁NO

154229-19-3

Solid

White to off-white

C[C@@]12C(C3=CN=CC=C3)=CC[C@]1([C@@]4(CC=C5[C@@](C)([C@]4(CC2)[H])CC[C@@H](C5)O)[H])[H]

Room temperature in continental US; may vary elsewhere.

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

• [1]. Attard G, et al. Phase I clinical trial of a selective inhibitor of CYP17, abiraterone acetate, confirms that castration-resistant prostate cancer commonly remains hormone driven. J Clin Oncol. 2008 Oct 1;26(28):4563-71.  [Content Brief]

  [2]. Richards J, et al. Interactions of abiraterone, eplerenone, and prednisolone with wild-type and mutant androgen receptor: a rationale for increasing abiraterone exposure or combining with MDV3100. Cancer Res. 2012 May 1;72(9):2176-82.  [Content Brief]

  [3]. Stein MN, et al. Androgen synthesis inhibitors in the treatment of castration-resistant prostate cancer. Asian J Androl. 2014 May-Jun;16(3):387-400.  [Content Brief]

  [4]. Li R, et al. Abiraterone inhibits 3β-hydroxysteroid dehydrogenase: a rationale for increasing drug exposure in castration-resistant prostate cancer. Clin Cancer Res. 2012 Jul 1;18(13):3571-9.  [Content Brief]

  [5]. Kumar SV, et al. Validated RP-HPLC/UV method for the quantitation of abiraterone in rat plasma and its application to a pharmacokinetic study in rats. Biomed Chromatogr. 2013 Feb;27(2):203-7.  [Content Brief]

  [6]. Stein MN, et al. Androgen synthesis inhibitors in the treatment of castration-resistant prostate cancer. Asian J Androl. 2014 May-Jun;16(3):387-400.  [Content Brief]