Galeterone

Galeterone is effective at preventing binding of [³H]-R1881 to the mutant LNCaP AR (T877A) with IC50 of 845 nM. Galeterone inhibits the DHT-induced proliferation of LNCaP and LAPC4 cells in a dose-dependent manner with IC50 of 6 μM and 3.2 μM, respectively. ^[1] Galeterone also inhibits the binding of [³H]-R1881 to the T575A mutant AR in PC3 cells with IC50 of 454 nM. Galeterone potently inhibits the proliferation of LNCaP and LAPC4 cells in the absence of DHT stimulation with IC50 of 2.6 μM and 4 μM, respectively. Furthermore, Galeterone treatment increases the degradation rate of the AR in a dose-dependent manner. ^[2] Galeterone potently inhibits the growth of the androgen-independent cell lines PC-3 and DU-145 in a dose-dependent manner with GI50 of 7.82 μM and 7.55 μM, respectively. Galeterone induces the endoplasmic reticulum stress response resulting in down-regulation of cyclin D1 protein expression and cyclin E2 mRNA. ^[3] Galeterone effectively inhibits proliferation of HP-LNCaP and C4-2B cell lines with IC50 of 2.9 μM and 9.7 μM, respectively. Galeterone treatment at 1 μM effectively inhibits androgen receptor activation in LNCaP cells (50%) and HP-LNCaP cells (70%). Galeterone decreases activation of the androgen receptor in both LNCaP cells and HP-LNCaP cells with IC50 of 1 μM and 411 nM, respectively, and down-regulates androgen receptor protein expression by 50% after 24 hour of treatment. ^[4] Galeterone reduces AR protein and mRNA expression, antagonizes AR-dependent promoter activation induced by androgen, and significantly reduces the phospho-4EBP1 levels. ^[6]