TOK-001 (Synonyms: TOK-001) |
Catalog No.GC13362
One-Click Copy Product Info
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TOK-001(TOK-001)은 거세 저항성 전립선암(CRPC)에서 다기능 항안드로겐 및 CYP17 억제제(IC50=47 nM)입니다.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 851983-85-2
Sample solution is provided at 25 µL, 10mM.
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TOK-001 (Galeterone) is a novel small molecule that selectively target CYP17 and androgen receptor for prostate cancer treatment [1].
CYP17 and androgen receptor (AR) are two preferred target during the treatment of prostate cancer: The former is the prime enzyme that responsible for the production of cancer-inducing androgens [1], whereas the latter acts as transcription factor that increases the expression of androgen-responsive genes [2].
Galeterone is a small molecular therapeutics that designed to treat prostate cancer in three distinctive pathways: competitively inhibit the enzyme function of CYP17. Decreasing androgen-responsive genes expression by binding to AR, and downregulates AR population [3]. Using 293T cells transfected with CYP17, galeterone inhibited the lyase function of CYP17 with an IC50 value of 47 nM after 18 hrs of incubation [3]. In prostate cancer cell line assay, galeterone inhibited the proliferation of LNCaP and LAPC-4 with IC50 value of 6 and 3 µM, respectively [3].
In mice xenograft model that inoculated with LAPC4 cell lines, a daily subcutaneous injection of galeterone (0.15 mmol/kg, twice per day) reduced both the average volume and weight of tumour less by more than 80% and 50%, respectively in comparison with control group [3]. Galeterone is currently underwent phase III clinical trails for castration-resistant prostate cancer.
References:
[1]. Devore N M, & Scott E E. Structures of cytochrome P450 17A1 with prostate cancer drugs abiraterone and TOK-001. Nature, 2012, 482: 116-119.
[2]. Mallik I, Davila M, Tapia T, et al. Androgen regulates Cdc6 transcription through interactions between androgen receptor and E2F transcription factor in prostate cancer cells. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2008,1783:1737-1744.
[3]. Bruno R D, Vasaitis T S, Gediya L. K, 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. Steroids, 2011,76: 1268-1279.
| Kinase experiment [1]: | |
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In vitro assay of CYP17 |
The in vitro CYP17 inhibitory activity of Galeterone was evaluated using rapid acetic acid releasing assay, utilizing intact P450c17-expressing E. coli as the enzyme source. It involved the use of [21-3H]-17α-hydroxypregnenolone as the substrate, and CYP17 activity was measured by the amount of tritiated acetic acid formed during the cleavage of the C-21 side chain of the substrate. IC50 value was obtained directly from plots relating percentage inhibition versus inhibitor concentration over appropriate ranges. |
| Cell experiment [2]: | |
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Cell lines |
LNCaP Cells |
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Preparation method |
The solubility of this compound in DMSO is > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
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Reacting condition |
1 ~ 15 μM; 24 hrs |
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Applications |
Compared with all Galeterone analogues, Galeterone was still the most effective compound in vitro, down-regulating > 95% AR at the concentration of 15 μM. |
| Animal experiment [2]: | |
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Animal models |
Male SCID mice bearing LAPC-4 tumors |
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Dosage form |
0.15 mmol/kg; s.c.; b.i.d., for 31 days |
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Applications |
Galeterone effectively inhibited the average volume of LAPC-4 tumors in SCID mice by more than 80%. After 31 days of Galeterone treatment, the final tumor weight was also significantly reduced by more than 50%. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Handratta VD, Vasaitis TS, Njar VC, Gediya LK, Kataria R, Chopra P, Newman D Jr, Farquhar R, Guo Z, Qiu Y, Brodie AM. Novel C-17-heteroaryl steroidal CYP17 inhibitors/antiandrogens: synthesis, in vitro biological activity, pharmacokinetics, and antitumor activity in the LAPC4 human prostate cancer xenograft model. J Med Chem. 2005 Apr 21;48(8):2972-84. [2]. Bruno R D, Vasaitis T S, Gediya L. K, 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. Steroids, 2011,76: 1268-1279. | |
| Cas No. | 851983-85-2 | SDF | |
| Synonyms | TOK-001 | ||
| 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 | ||
| Canonical SMILES | CC12CCC(CC1=CCC3C2CCC4(C3CC=C4N5C=NC6=CC=CC=C65)C)O | ||
| Formula | C26H32N2O | M.Wt | 388.56 |
| Solubility | ≥ 12.4mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.5736 mL | 12.868 mL | 25.7361 mL |
| 5 mM | 514.7 μL | 2.5736 mL | 5.1472 mL |
| 10 mM | 257.4 μL | 1.2868 mL | 2.5736 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 34 reference(s) in Google Scholar.)