For research use only. Not for therapeutic Use.
Galeterone (TOK-001) is a multifunctional antiandrogen and CYP17 inhibitor (IC50=47 nM) in castration resistant prostate cancer (CRPC).
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 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 Galeterone (TOK-001), the steady-state levels of AR protein are markedly decreased (up to 84%, 15 μM 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 μM. When LNCaP cells are treated with 20 μM TOK-001 for 24 h, AR mRNA levels are reduced by 38%[3].
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].
| Catalog Number | I005114 |
| CAS Number | 851983-85-2 |
| Synonyms | (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 |
| Molecular Formula | C26H32N2O |
| Purity | ≥95% |
| InChI | InChI=1S/C26H32N2O/c1-25-13-11-18(29)15-17(25)7-8-19-20-9-10-24(26(20,2)14-12-21(19)25)28-16-27-22-5-3-4-6-23(22)28/h3-7,10,16,18-21,29H,8-9,11-15H2,1-2H3/t18-,19-,20-,21-,25-,26-/m0/s1 |
| InChIKey | PAFKTGFSEFKSQG-PAASFTFBSA-N |
| SMILES | CC12CCC(CC1=CCC3C2CCC4(C3CC=C4N5C=NC6=CC=CC=C65)C)O |
| Reference | [1]. Bruno RD, et al. Synthesis and biological evaluations of putative metabolically stable analogs of VN/124-1 (TOK-001): head to head anti-tumor efficacy evaluation of VN/124-1 (TOK-001) and abiraterone in LAPC-4 human prostate cancer xenograft model.Steroid [2]. DeVore NM, et al. Structures of cytochrome P450 17A1 with prostate cancer drugs abiraterone and TOK-001.Nature. 2012 Jan 22;482(7383):116-9. [3]. Soifer HS, et al. Direct regulation of androgen receptor activity by potent CYP17 inhibitors in prostate cancer cells.J Biol Chem. 2012 Feb 3;287(6):3777-87. Epub 2011 Dec 15. |
