tcsc0544 Abiraterone (acetate)

Abiraterone acetate is an oral, potent, selective, and irreversible inhibitor of CYP17.

IC50 & Target: CYP17^[1]

In Vitro: Abiraterone (Abi) acetate is an ester prodrug of the anticancer agent Abiraterone, which 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^[1].

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 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 Abiraterone significantly inhibited CRPC progression in the robustly growing subset, effectively putting a ceiling on tumor growth over 4 weeks of treatment (P<0.00001)^[3].

In Vivo: Abiraterone (Abi) acetate prolongs survival in castration-resistant prostate cancer (CRPC). [³H]-dehydroepiandrosterone (DHEA) depletion and Δ⁴-androstenedione (AD) accumulation are inhibited by Abiraterone in LNCaP, with an IC₅₀<1 μM. 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^[3].