Galeterone

851983-85-2

C26H32N2O

DMSO : 18 mg/mL (46.33 mM; Need ultrasonic and warming)

Metabolic Enzyme/Protease

Galeterone (TOK-001) is a multifunctional antiandrogen and CYP17 inhibitor (IC₅₀=47 nM) in castration resistant prostate cancer (CRPC). IC50 & Target: IC50: 47 nM (CYP17)^[1] In Vitro: Galeterone (TOK-001) affords strong CYP17 lyase inhibition, with IC₅₀ of 47 nM^[1]. Galeterone (TOK-001) is both a CYP17A1 inhibitor and androgen receptor antagonist and the similarity of these binding modes is likely the reason for this dual mechanism of action.This CYP17A1 binds abiraterone and Galeterone (TOK-001) with absorbance decreases at 402 nm and increases at 424 nm, consistent with nitrogen binding to the heme iron (type II interaction) with K_d of <100 nM^[2]. When LNCaP cells are cultured in medium supplemented with charcoal-stripped serum (CSS, T<1 nM) followed by treatment with increasing concentrations of Galeterone (TOK-001), the steady-state levels of AR protein are markedly decreased (up to 84%, 15 uM Galeterone (TOK-001)). In LAPC-4 cells, abiraterone alcohol reduced AR expression to a greater extent than Galeterone (TOK-001) at concentrations greater than or equal to 1 uM. When LNCaP cells are treated with 20 uM TOK-001 for 24 h, AR mRNA levels are reduced by 38%^[3]. In Vivo: Mice inoculated with LAPC-4 tumors are treated subcutaneously with 0.15 mmol/kg of Galeterone (TOK-001) twice daily. Mice treated with TOK-001 have smaller average tumor volume on day 31 when compared to control (p= 0.0001). Galeterone (TOK-001) treatment also significantly reduces the growth rate of tumor growth compared to control (p<0.0001). Upon excision, final tumor weights are also significantly reduced in animals treated with Galeterone (TOK-001) compared to animals treated with control, and castration (p<0.05)^[1].