Apalutamide

Apalutamide is a pivotal active pharmaceutical ingredient and certified reference standard for quality control of this androgen receptor inhibitor. The thiohydantoin core of Apalutamide is constructed through a multi-step synthetic sequence. In quality control contexts, Apalutamide and its related impurities—including N-desmethyl apalutamide (active metabolite)—are essential analytical reference standards for impurity profiling and analytical method development. As an orally administered AR inhibitor, Apalutamide represents a significant therapeutic advance for prostate cancer.

Product Parameters

Bioactivity

Apalutamide (ARN-509) is a selective, competitive androgen receptor inhibitor with an IC50 of 16 nM in cell-free assays, and is effective in the treatment of prostate cancer. Phase 3.

In Vitro Study

In the LNCaP/AR prostate cancer cell line, ARN-509 (<10μM) inhibits the androgen-mediated induction or suppression of the mRNA expression levels of 13 endogenous genes, including PSA and TMPRSS2. ARN-509 (<10μM) inhibits the proliferation effect of R1881 (30pM) in the LNCaP/AR prostate cancer cell line. In LNCaP cells expressing AR-EYFP, ARN-509 (10μM) disrupts the nuclear localization of AR, thereby reducing the concentration of AR bound to androgen response elements. 10μM ARN-509 can effectively compete with 1nM R1881, thereby preventing AR from binding to the promoter region. In Hep-G2 cells expressing the VP16-AR fusion protein and the ARE-driven luciferase reporter gene system, ARN-509 inhibits R1881-induced VP16-AR-mediated transcription, with an IC50 of 0.2μM

In vivo study

In a mouse model of castrated male immunodeficient mice bearing LNCaP/AR-luc xenograft tumors, ARN-509 (10 mg/kg/day, oral administration) inhibits tumor growth, which is manifested as a decreased proliferation rate and an increased apoptosis rate. For castrated male immunodeficient mice bearing LNCaP/AR-luc xenograft tumors, ARN-509 exerts the optimal inhibitory effect on tumor growth at a dose of 30 mg/kg/day, and the inhibitory effect is dose-dependent. Treatment with ARN-509 at a dose of 10 mg/kg/day for 28 days can reduce the weight of the prostate lacking glandular secretory activity by 3-fold and reduce the testicular weight of adult male dogs by 1.7-fold. ARN-509 (10 mg/kg/day, oral administration) inhibits cell proliferation in the prostate tissue of adult male dogs. Among 24 patients with metastatic CRPC who had received prior treatment, ARN-509 is safe and well tolerated, with the peak plasma concentration occurring 2 to 3 hours after administration. In patients with metastatic CRPC, ARN-509 induces a sustained decrease in PSA within the dose range of 30 to 300 mg. In a mouse model of castration-resistant prostate cancer, ARN-509 has strong anti-cancer activity and can induce long-term symptomatic remission after the completion of treatment.

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For Apalutamide inquiries related to your prostate cancer therapeutic development or analytical program, Cosperpharm is ready to assist with reliable supply and technical support.