WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 205646
Description: Galeterone, also known as TOK-001 and NX41765; is an orally bioavailable small-molecule androgen receptor modulator and CYP17 lyase inhibitor with potential antiandrogen activity. Galeterone exhibits three distinct mechanisms of action: 1) as an androgen receptor antagonist, 2) as a CYP17 lyase inhibitor and 3) by decreasing overall androgen receptor levels in prostate cancer tumors, all of which may result in a decrease in androgen-dependent growth signaling.
MedKoo Cat#: 205646
Chemical Formula: C26H32N2O
Exact Mass: 388.25146
Molecular Weight: 388.54508
Elemental Analysis: C, 80.37; H, 8.30; N, 7.21; O, 4.12
Synonym: TOK001; TOK 001; TOK-001; NX41765; NX 41765; NX-41765; VN 1241; VN-1241; VN-1241; Galeterone.
IUPAC/Chemical Name: (3S,8R,9S,10R,13S,14S)-17-(1H-benzo[d]imidazol-1-yl)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol
InChi Key: PAFKTGFSEFKSQG-PAASFTFBSA-N
InChi Code: 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
SMILES Code: O[C@H]1CC[C@]2(C)[C@@]3([H])CC[C@]4(C)C(N5C=NC6=CC=CC=C56)=CC[C@@]4([H])[C@]3([H])CC=C2C1
Appearance: White to off white solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
|Biological target:||Galeterone (TOK-001) is a selective CYP17 inhibitor and androgen receptor (AR) antagonist with an IC50 of 300 nM and 384 nM, respectively.|
|In vitro activity:||The effectiveness of galeterone as single drug alone on viability, growth and migration of breast cancer cell lines was evaluated. Normal breast cells were used as normal control. Exposure to galeterone at 0.25 to 16 μM dose-dependently decreased viability of six breast cancer cell lines (Fig. 1a). Galeterone inhibited proliferation in these cells as assessed by labelling BrdU (a proliferative marker), with IC50 from 0.5 to 4 μM (Fig. 1b and Supplementary Table 1). It was found that galeterone also significantly inhibited proliferation of normal breast cells, but to a lesser extent than in breast cancer cells (Supplementary Fig. 1 and Supplementary Table 1). The IC50 of galeterone on normal breast cells are 9.5 μM and 15.7 μM, which is > tenfold higher than the IC50 of the most sensitive breast cancer cell lines tested in our study. In addition, galeterone inhibited breast cancer cell migration with IC50 > 4 μM (Fig. 1c, d). The results demonstrated that (1) galeterone at nanomolar concentration is active against breast cancer cells regardless of subtypes and genetic profiles; (2) IC50 of galeterone varies among breast cancer cell lines, with MDA-MB-231 being most sensitive and MCF-7 most resistant; (3) galeterone has preferential anti-proliferative activity to breast cancer cells compared to normal counterparts; (4) galeterone is more effective in inhibiting growth and survival than cell migration. Reference: Cancer Chemother Pharmacol. 2021 Jan;87(1):85-93. https://dx.doi.org/10.1007/s00280-020-04195-w|
|In vivo activity:||The in vivo efficacy of galeterone alone was evaluated. A breast cancer xenograft mouse model was generated by subcutaneously injecting MDA-MB-231 cells to mice flank. After development of palpable tumor, drug treatment started and tumor size was monitored for signs of possible toxicity due to treatment. No significant weight loss, abnormality in appearance or behavior in mice was observed suggesting that the treatment given to mice are not toxic. Notably, oral galeterone at 150 mg/kg significantly inhibited breast cancer growth in vivo (Fig. 5a). Reference: Cancer Chemother Pharmacol. 2021 Jan;87(1):85-93. https://dx.doi.org/10.1007/s00280-020-04195-w|
|Solvent||Max Conc. mg/mL||Max Conc. mM|
The following data is based on the product molecular weight 388.54508 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||1.15 mL||5.76 mL||11.51 mL|
|5 mM||0.23 mL||1.15 mL||2.3 mL|
|10 mM||0.12 mL||0.58 mL||1.15 mL|
|50 mM||0.02 mL||0.12 mL||0.23 mL|
|In vitro protocol:||1. Xu Y, Liao S, Wang L, Wang Y, Wei W, Su K, Tu Y, Zhu S. Galeterone sensitizes breast cancer to chemotherapy via targeting MNK/eIF4E and β-catenin. Cancer Chemother Pharmacol. 2021 Jan;87(1):85-93. doi: 10.1007/s00280-020-04195-w. Epub 2020 Nov 7. PMID: 33159561. 2. Kwegyir-Afful AK, Ramalingam S, Purushottamachar P, Ramamurthy VP, Njar VC. Galeterone and VNPT55 induce proteasomal degradation of AR/AR-V7, induce significant apoptosis via cytochrome c release and suppress growth of castration resistant prostate cancer xenografts in vivo. Oncotarget. 2015 Sep 29;6(29):27440-60. doi: 10.18632/oncotarget.4578. PMID: 26196320; PMCID: PMC4695001.|
|In vivo protocol:||1. Xu Y, Liao S, Wang L, Wang Y, Wei W, Su K, Tu Y, Zhu S. Galeterone sensitizes breast cancer to chemotherapy via targeting MNK/eIF4E and β-catenin. Cancer Chemother Pharmacol. 2021 Jan;87(1):85-93. doi: 10.1007/s00280-020-04195-w. Epub 2020 Nov 7. PMID: 33159561. 2. Kwegyir-Afful AK, Ramalingam S, Purushottamachar P, Ramamurthy VP, Njar VC. Galeterone and VNPT55 induce proteasomal degradation of AR/AR-V7, induce significant apoptosis via cytochrome c release and suppress growth of castration resistant prostate cancer xenografts in vivo. Oncotarget. 2015 Sep 29;6(29):27440-60. doi: 10.18632/oncotarget.4578. PMID: 26196320; PMCID: PMC4695001.|
1: Gomez L, Kovac JR, Lamb DJ. CYP17A1 inhibitors in castration-resistant prostate cancer. Steroids. 2015 Jan 3. pii: S0039-128X(14)00314-6. doi: 10.1016/j.steroids.2014.12.021. [Epub ahead of print] PubMed PMID: 25560485.
2: Gupta E, Guthrie T, Tan W. Changing paradigms in management of metastatic Castration Resistant Prostate Cancer (mCRPC). BMC Urol. 2014 Jul 25;14:55. doi: 10.1186/1471-2490-14-55. PubMed PMID: 25062956; PubMed Central PMCID: PMC4167156.
3: Yu Z, Cai C, Gao S, Simon NI, Shen HC, Balk SP. Galeterone prevents androgen receptor binding to chromatin and enhances degradation of mutant androgen receptor. Clin Cancer Res. 2014 Aug 1;20(15):4075-85. doi: 10.1158/1078-0432.CCR-14-0292. Epub 2014 May 29. PubMed PMID: 24874833; PubMed Central PMCID: PMC4119496.
4: Stein MN, Patel N, Bershadskiy A, Sokoloff A, Singer EA. Androgen synthesis inhibitors in the treatment of castration-resistant prostate cancer. Asian J Androl. 2014 May-Jun;16(3):387-400. doi: 10.4103/1008-682X.129133. Review. PubMed PMID: 24759590; PubMed Central PMCID: PMC4023364.
5: Agarwal N, Di Lorenzo G, Sonpavde G, Bellmunt J. New agents for prostate cancer. Ann Oncol. 2014 Sep;25(9):1700-9. doi: 10.1093/annonc/mdu038. Epub 2014 Mar 20. PubMed PMID: 24658665.
6: Neuzillet Y, Flamand V, Lebdai S, Villers A, Lebret T. [Prostate cancer and new hormonal treatments: mechanism of action and main clinical results]. Prog Urol. 2013 Oct;23 Suppl 1:S34-43. doi: 10.1016/S1166-7087(13)70044-7. Review. French. PubMed PMID: 24314737.
7: Yin L, Hu Q. CYP17 inhibitors--abiraterone, C17,20-lyase inhibitors and multi-targeting agents. Nat Rev Urol. 2014 Jan;11(1):32-42. doi: 10.1038/nrurol.2013.274. Epub 2013 Nov 26. Review. PubMed PMID: 24276076.
8: Pinto Ã
Galeterone (TOK-001 or VN/124-1) is a novel antiandrogen under development by Tokai Pharmaceuticals for the treatment of prostate cancer. It possesses a unique dual mechanism of action, acting as both an androgen receptor antagonist and an inhibitor of CYP17A1, an enzyme required for the biosynthesis of the androgens. As of the second half of 2014, galeterone is in phase III clinical trials for castration-resistant prostate cancer.
Localized to the endoplasmic reticulum (ER), the cytochrome P450 enzyme CYP17 (P450C17 or CYP17A1) exhibits both 17alpha-hydroxylase and 17,20-lyase activities, and plays a key role in the steroidogenic pathway that produces progestins, mineralocorticoids, glucocorticoids, androgens, and estrogens.