Proxalutamide is a potent antagonist of the androgen receptor (AR).

Proxalutamide inhibits the proliferation of hormone-sensitive CaP cells and more potently inhibits the proliferation of CRPC cells. Proxalutamide inhibits the growth of AR-positive breast cancer cells. Proxalutamide more effectively inhibits androgen binding with AR's ligand-binding domain than Bicalutamide (11.4x) and MDV3100 (3.5x). Proxalutamide displays stronger potency to block AR function of gene transcription than Bicalutamide (~5-10) and MDV3100 (2-5x) while maintaining full antagonism in CRPC cells, in both hormone-sensitive (LNCaP) and CRPC (C4-2) cancer cells. Proxalutamide has minimum effects on the growth of AR-negative CaP cells (PC-3 and DU145), showing it is a selective AR pathway inhibitor. Proxalutamide impairs androgen stimulates AR translocation to cell nuclei hence blocks its binding DNA and shuts down the downstream oncogenic signaling and Proxalutamide also causes AR downregulation in prostate cancer cells [1].

The mean Proxalutamide (GT0918) half-life estimate from the pHM-SD tablets (7.9±2.2 h) was similar to that of the conventional tablets (8.4±0.5 h), remaining consistent with the following pharmacokinetic theory: the extent and rate of absorption should not affect elimination. The relative bioavailability (frel) of the pHM-SD tablets is 125.6% of that for the conventional tablets on average, revealing that the bioavailability of the former is higher. The tmax for the pHM-SD and conventional tablets are 0.9±0.4 h and 2.5±1.1 h, respectively, meaning that the pHM-SD tablets dissolve more quickly than the conventional tablets. The mean Cmax and the AUC0-36 are 5.1±2.4 μg/mL and 38.3±8.2 μgh/mL for the pHM-SD tablets versus 3.1±1.5 μg/mL and 42.1±22.3 μgh/mL for conventional tablets, respectively [2].