TOK-001(Galeterone)

Cas No.:	851983-85-2
Chemical Name:	(3S,8R,9S,10R,13S,14S)-17-(benzimidazol-1-yl)-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15-decahydro-1H-cyclopenta[a]phenanthren-3-ol
Synonyms:	VN/124-1; Galeterone，TOK001，TOK 001，TOK-001
SMILES:	C[C@]12CC[C@@H](CC1=CC[C@@H]3[C@@H]2CC[C@]4([C@H]3CC=C4N5C=NC6=CC=CC=C65)C)O
Formula:	C26H32N2O
M.Wt:	388.55
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	TOK-001 is a multifunctional antiandrogen and CYP17 inhibitor (IC50=47 nM) in castration resistant prostate cancer (CRPC).
In Vivo:	Mice inoculated with LAPC-4 tumors are treated subcutaneously with 0.15 mmol/kg of TOK-001 twice daily. Mice treated with TOK-001 have smaller average tumor volume on day 31 when compared to control (p= 0.0001). 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 TOK-001 compared to animals treated with control, and castration (p<0.05)[1].
In Vitro:	TOK-001 affords strong CYP17 lyase inhibition, with IC50 of 47 nM[1]. 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 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 Kd 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 TOK-001, the steady-state levels of AR protein are markedly decreased (up to 84%, 15 μM TOK-001). In LAPC-4 cells, abiraterone alcohol reduced AR expression to a greater extent than TOK-001 at concentrations greater than or equal to 1 μM. When LNCaP cells are treated with 20 μM TOK-001 for 24 h, AR mRNA levels are reduced by 38%[3].