Molecular Formula | C21H15F4N5O2S |
Molar Mass | 477.43 |
Density | 1.59±0.1 g/cm3(Predicted) |
pKa | 13.83±0.46(Predicted) |
Storage Condition | -20℃ |
In vitro study | ARN-509 (< 10 μm) Inhibited Androgen-mediated induction or repression of mRNA expression levels of 13 endogenous genes, including PSA and TMPRSS2, in the LNCaP/AR prostate cancer cell line. ARN-509 (< 10 μm) inhibits the proliferative effect of R1881 (30 pM) in the LNCaP/AR prostate cancer cell line. In AR-EYFP-expressing LNCaP cells, ARN-509 (10 μm) disrupts the nuclear localization of AR and thus decreases the concentration of AR bound to androgen response elements. 10 μm ARN-509 can effectively compete with 1 nM R1881 to prevent AR binding to the promoter region. ARN-509 represses r1881-induced VP16-AR-mediated transcriptional levels with an IC50 of 0.2 μm in Hep-G2 cells expressing the VP16-AR fusion protein and in a rasp-driven luciferase reporter system |
In vivo study | ARN-509 (10 mg/kg/day P. O.) inhibits tumor growth in a male-castrated immunodeficient mouse model bearing LNCaP/AR-luc xenograft tumors, it showed a decrease in proliferation rate and an increase in apoptosis rate. Tumor growth inhibition was best ARN-509 at a dose of 30 mg/kg/day in castrated male immunodeficient mice bearing LNCaP/AR-luc xenograft tumors, the inhibitory effect has a dose-dependent character. Treatment with ARN-509 at a dose of 10 mg/kg/day for 28 days resulted in a 3-fold reduction in the weight of the prostate, which lacked glandular secretory activity, and a 1.7-fold reduction in the weight of the testes in adult male dogs. ARN-509 (10 mg/kg/day, P. O.) inhibits cell proliferation in adult male dog prostate tissue. The ARN-509 was safe and well tolerated in 24 patients with metastatic CRPC who had already received prior treatment, with peak blood levels occurring 2 to 3 hours after administration. ARN-509 in the 30 to 300 mg dose range resulted in a sustained decrease in PSA in patients with metastatic CRPC. ARN-509 has potent anti-cancer activity and induces long-term remission after completion of treatment in a castration-resistant prostate cancer mouse model |
1mg | 5mg | 10mg | |
---|---|---|---|
1 mM | 2.095 ml | 10.473 ml | 20.945 ml |
5 mM | 0.419 ml | 2.095 ml | 4.189 ml |
10 mM | 0.209 ml | 1.047 ml | 2.095 ml |
5 mM | 0.042 ml | 0.209 ml | 0.419 ml |