TAK-733 |
Catalog No.GC10209
One-Click Copy Product Info
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TAK-733 es un inhibidor del sitio alostérico MEK potente y selectivo con una IC50 de 3,2 nM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1035555-63-5
Sample solution is provided at 25 µL, 10mM.
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TAK-733 is a potent, ATP-noncompetitive and selective inhibitor of MEK allosteric site with the IC50 value of 3.2nM [1].
TAK-733 has been shown potent enzymatic and cell activity with an IC50 value of 3.2nM against constitutively active MEK enzyme and an EC50 of 1.9nM against ERK phosphorylation in cells. In addition, TAK-733 has also shown the low clearance and high oral bioavailability based on the pharmacokinetics of TAK-733 in all species (Mouse, rat, dog and Monkey). Furthermore, TAK-733 has been reported to broad inhibit tumor activity in mouse xenograft models of human cancer (melanoma, colorectal, NSCLC, pancreatic and breast cancer) [1].
References:
[1] Dong Q1, Dougan DR, Gong X, Halkowycz P, Jin B, Kanouni T, O'Connell SM, Scorah N, Shi L, Wallace MB, Zhou F. Discovery of TAK-733, a potent and selective MEK allosteric site inhibitor for the treatment of cancer. Bioorg Med Chem Lett. 2011 Mar 1;21(5):1315-9. doi: 10.1016/j.bmcl.2011.01.071. Epub 2011 Jan 22.
| Cell experiment : | |
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Cell lines |
Human cutaneous melanoma cell lines; Colorectal cancer (CRC) cell lines |
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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℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
0.01-0.125 μM; 72h |
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Applications |
TAK-733 showed broad activity in most melanoma cell lines with relative resistance observed at IC50 > 0.1 μmol/L in vitro [1]. Moreover, Cell lines with a BRAF or KRAS mutation were associated with sensitivity to TAK-733 with an IC50 value of < 0.5μM [2]. |
| Animal experiment [1]: | |
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Animal models |
Mice bearing A375 human melanoma xenografts; patient-derived CRC xenograft models |
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Dosage form |
1, 3, 10, or 35 mg/kg; oral gavage; once daily for 2 weeks; or 10 mg/kg; oral gavage, once daily for 28 days. |
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Applications |
TAK-733 showed statistically significant tumor growth inhibition in patient-derived xenograft models [1]. Moreover, TAK-733 induced tumor growth inhibition and MEK pathway inhibition in patient-derived CRC xenografts [2]. |
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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. Micel, L. N., Tentler, J. J., Tan, A. C., Selby, H. M., Brunkow, K. L., Robertson, K. M., Davis, S. L., Klauck, P. J., Pitts, T. M., Gangolli, E., Fabrey, R., O'Connell, S. M., Vincent, P. W. and Eckhardt, S. G. (2015) Antitumor activity of the MEK inhibitor TAK-733 against melanoma cell lines and patient-derived tumor explants. Mol Cancer Ther. 14, 317-325 2. Lieu, C. H., Klauck, P. J., Henthorn, P. K., Tentler, J. J., Tan, A. C., Spreafico, A., Selby, H. M., Britt, B. C., Bagby, S. M., Arcaroli, J. J., Messersmith, W. A., Pitts, T. M. and Eckhardt, S. G. (2015) Antitumor activity of a potent MEK inhibitor, TAK-733, against colorectal cancer cell lines and patient derived xenografts. Oncotarget. 6, 34561-34572 | |
| Cas No. | 1035555-63-5 | SDF | |
| Chemical Name | 3-[(2R)-2,3-dihydroxypropyl]-6-fluoro-5-(2-fluoro-4-iodoanilino)-8-methylpyrido[2,3-d]pyrimidine-4,7-dione | ||
| Canonical SMILES | CN1C2=C(C(=C(C1=O)F)NC3=C(C=C(C=C3)I)F)C(=O)N(C=N2)CC(CO)O | ||
| Formula | C17H15F2IN4O4 | M.Wt | 504.23 |
| Solubility | ≥ 25.2mg/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 | 1.9832 mL | 9.9161 mL | 19.8322 mL |
| 5 mM | 396.6 μL | 1.9832 mL | 3.9664 mL |
| 10 mM | 198.3 μL | 991.6 μL | 1.9832 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: >99.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 9 reference(s) in Google Scholar.)