Galeterone

Galeterone (TOK-001) is a potent, orally active molecular glue degrader, which degrades androgen receptor (AR) and its splice variants (AR-Vs) and MAP kinase-interacting serine/threonine protein kinase Mnk1/2. Galeterone also functions as a CYP17 inhibitor (IC₅₀ = 47 nM). Galeterone induces cell apoptosis. Galeterone inhibits tumor growth in human prostate cancer xenograft mouse models. Galeterone can be used for castration resistant prostate cancer (CRPC) and pancreatic ductal adenocarcinoma (PDAC) research^[1][2]. IC50 & Target:IC50: 47 nM (CYP17)^[1] In Vitro:Galeterone (compound 1) possess potent antiproliferative activities with GI₅₀ of 2.43 μM, 2.20 μM, 3.80 μM against LNCaP (androgen-sensitive), C42B (androgen-insensitive) and CWR22Rv1 (castration-resistant), respectively^[1].
Galeterone (5-20 μM; 24 h) can degrade AR/AR-V7 and Mnk1/2 with consequent inhibition of AR signaling and depletion of peIF4E, respectively, and modulation of the downstream molecular targets in human CWR22Rv1 prostate cancer cell^[1].
Galeterone (compound 5) (1-15 μM, 24 h) causes AR down-regulation in LNCaP cells, with nearly complete (>95%) AR down-regulation at 15 μM^[2]. In Vivo:Galeterone (compound 1) (100 mg/kg; p.o.; b.i.d.; 5 days per/week; for 16 days) shows antitumor activity in CWR22Rv1 tumor xenograft^[1].
Galeterone (compound 5) (0.15 mmol/kg; s.c.; b.i.d. for 31 days) shows antitumor activity in a LAPC-4 xenograft mouse model^[2].