Abiraterone Acetate

391, 55

Male NOD/SCID mice with LAPC4 cells

Abiraterone has entered in a phase II clinical trial in the treatment of castration-resistant prostate cancer and stage IV prostate cancer.

0.5 mmol/kg/d

72 nM [1], 72 nM [1], 72 nM [1], 72 nM [1], 72 nM [1], 72 nM [1]

At doses of 100 mg/kg, Erlotinib HCl completely prevents EGF-induced autophosphorylation of EGFR in human HN5 tumors growing as xenografts in athymic mice and of the hepatic EGFR of the treated mice.[2] Erlotinib HCl (100 mg/Kg) inhibits H460a and A549 tumor models with 71 and 93% inhibition rate.[6]

[3], C17, 20-lyase activity assay, Microsomes are diluted to a final protein concentration of 50 ug/mL in the reaction mixture which contains 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, test compounds are 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 in our laboratory using a specific antibody against delta4A and instructions provided by Biogenesis. The separation of free and bound antigen is achieved with a dextran-coated charcoal suspension. After centrifugation, aliquots of the clear supernatant are counted in duplicates in a 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 20 mg/mL, Water <1 mg/mL, Ethanol 78 mg/mL

(3S, 8R, 9S, 10R, 13S, 14S)-10, 13-dimethyl-17-(pyridin-3-yl)-2, 3, 4, 7, 8, 9, 10, 11, 12, 13, 14, 15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate