Abiraterone

349, 51

LAPC-4 xenograft mice

Abiraterone acetate plus prednisone has entered in a phase II clinical trial in the treatment of prostate cancer.

0.15 mmol/kg

2 nM [1], 2 nM [1], 2 nM [1], 2 nM [1], 2 nM [1], 2 nM [1]

Abiraterone inhibits CYP17 with an IC50 of 72 nM, in human testicular microsomes. [4] Abiraterone fails to significantly reduce the size of any of the organs. [5] Abiraterone reduces the testosterone levels strongly, almost reaching the level of the orchiectomy control. The testosterone levels are reduced by Abiraterone for more than 95% compared to the control group. [6]

[3], C17, 20-lyase activity assay, Microsomes are diluted to a final protein concentration of 50 ug/mL in the reaction mixture which contained 0.25 M sucrose, 20 mM Tris–HCl (pH 7.4), 10 mM G6P and 1.2 IU/mL G6PDH. After equilibration at 37 C for 10 minutes, the reaction is initiated by addition of betaNADP to obtain a final concentration of 0.6 mM. Prior to the distribution of 600 uL of the reaction mixture in each tube, Abiraterone is evaporated to dryness under a stream of nitrogen and then are incubated at 37 C for 10 minutes. After incubation with Abiraterone, 500 uL of the reaction mixture is transferred to tubes containing 1 uM of the enzyme substrate, 17OHP. After a further 10 minutes incubation, tubes are placed on ice and the reaction is stopped by addition of 0.1 ml NaOH 1N. Tubes are deep-frozen and stored at 20 C until assayed for delta4A levels. A delta4A RIA is developed and automated on a microplate format using a specific antibody against delta4A. The separation of free and bound antigen achieved with a dextran-coated charcoal suspension. After centrifugation, aliquots of the clear supernatant are counted in duplicates in a 1450 MicrobetaPlus liquid scintillation counter. The delta4A concentrations of unknown samples are determined from the standard curve. The detection limit is 0.5 ng/mL and the within and between assay coefficients of variation are 10.7 and 17.6%, respectively at an assay value of 13 ng/mL. The rate of enzymatic reaction is expressed as pmol of delta4A formed per 10 minutes and per mg of protein. The value of maximum activity without inhibitor (control) is set at 100%. The IC50 values are calculated using non-linear analysis from the plot of enzyme activity (%) against log of inhibitor concentration.

DMSO 0.33 mg/mL, Water <1 mg/mL, Ethanol <1 mg/mL

Abiraterone has been approved for the treatment of docetaxel-treated castration-resistant prostate cancer (CRPC).