Abiraterone

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

Abiraterone (CB-7598) 是一种有效的类固醇细胞色素 P450 17α-羟化酶-17,20-裂合酶 (CYP17) 抑制剂，IC50 为 4 nM。

Abiraterone (CB-7598) is a potent steroidal cytochrome P450 17alpha-hydroxylase-17,20-lyase (CYP17) inhibitor with an IC50 at 4 nM.(In Vitro):Significant inhibition of proliferation of the AR-positive prostate cancer cell lines LNCaP and VCaP with doses of Abiraterone ≥5 μM is confirmed. 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. Abiraterone inhibits recombinant human 3βHSD1 and 3βHSD2 activity with competitive Ki 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.(In Vivo):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. Following i.v. administration (5 mg/kg) the clearance (Cl) and volume of distribution (Vd) are found to be 31.2 mL/min/kg and 1.97 L/kg, respectively. The AUC0-∞ (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 (t1/2) is 0.73 h. Because of high clearance, Abiraterone (ART) is quantifiable only until 2 h following i.v. administration.

Significant inhibition of proliferation of the AR-positive prostate cancer cell lines LNCaP and VCaP with doses of Abiraterone ≥5 μM is confirmed. 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. Abiraterone inhibits recombinant human 3βHSD1 and 3βHSD2 activity with competitive Ki 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.

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. Following i.v. administration (5 mg/kg) the clearance (Cl) and volume of distribution (Vd) are found to be 31.2 mL/min/kg and 1.97 L/kg, respectively. The AUC0-∞ (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 (t1/2) is 0.73 h. Because of high clearance, Abiraterone (ART) is quantifiable only until 2 h following i.v. administration.

CB-7598

Metabolic Enzyme/Protease

P450

CYP17

Cancer

Prostate Cancer

154229-19-3

349.51

C24H31NO

>98% (HPLC)

Ethanol: 0.2 mg/mL (0.57 mM); Water: 0.02 mg/mL (0.05 mM); DMSO: 0.1 mg/mL (0.28 mM)

C[C@]12CC[C@@H](CC1=CC[C@@H]3[C@@H]2CC[C@]4([C@H]3CC=C4C5=CN=CC=C5)C)O

——

(-20℃)

With Ice Pack

≥ 2 years