TAK-733
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.
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 504.23 |
| Cas No. | 1035555-63-5 |
| Formula | C17H15F2IN4O4 |
| Solubility | ≥25.2 mg/mL in DMSO; insoluble in EtOH; insoluble in H2O |
| Chemical Name | 3-[(2R)-2,3-dihydroxypropyl]-6-fluoro-5-(2-fluoro-4-iodoanilino)-8-methylpyrido[2,3-d]pyrimidine-4,7-dione |
| SDF | Download SDF |
| 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 |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| 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 | |
| Description | TAK-733 is a potent and selective inhibitor of MEK allosteric site for MEK1 with an IC50 value of 3.2 nM. | |||||
| Targets | MEK1 | |||||
| IC50 | 3.2 nM | |||||
Quality Control & MSDS
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Chemical structure
