Trametinib (GSK1120212)
Trametinib (GSK1120212; CAS 871700-17-3) is a small molecule inhibitor targeting MEK1 and MEK2 kinases. It exhibits an ATP-noncompetitive mechanism, thereby suppressing the phosphorylation and activation of ERK1/2 signaling proteins. Through MEK-ERK pathway inhibition, trametinib induces p15 and p27 expression, downregulates cyclin D1 and thymidylate synthase (TS), promotes RB protein hypophosphorylation, and results in G1 phase cell cycle arrest. Research demonstrates trametinib's antitumor activity in various xenograft models and enhanced sensitivity in B-RAF mutated cell lines, highlighting its importance as a tool in oncology research.
Reference
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Motoki Watanabe, Yoshihiro Sowa, Mayumi Yogosawa and Toshiyuki Sakai. Novel MEK inhibitor trametinib and other retinoblastoma gene (RB)-reactivating agents enhance efficacy of 5-fluorouracil on human colon cancer cells. Cancer Sci 2013; 104(6): 687-693
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| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 615.39 |
| Cas No. | 871700-17-3 |
| Formula | C26H23FIN5O4 |
| Synonyms | Trametinib, GSK-1120212, GSK1120212, Mekinist, JTP74057, JTP-74057 |
| Solubility | insoluble in H2O; insoluble in EtOH; ≥15.38 mg/mL in DMSO |
| Chemical Name | N-[3-[3-cyclopropyl-5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]acetamide |
| SDF | Download SDF |
| Canonical SMILES | CC1=C2C(=C(N(C1=O)C)NC3=C(C=C(C=C3)I)F)C(=O)N(C(=O)N2C4=CC(=CC=C4)NC(=O)C)C5CC5 |
| 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: [1] | |
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Cell lines |
HT-29 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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Reaction Conditions |
100 nM, 72 hours |
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Applications |
Trametinib showed a subnanomolar IC50 value for 72 h in a Cell Counting Kit-8 assay of human colon cancer HT-29 cells. The treatment with trametinib for 24 h dose-dependently increased the G1 phase with a decrease in the S phase, and 72 h treatment induced apoptosis in a dose-dependent manner together with G1 arrest. |
| Animal experiment: [2] | |
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Animal models |
Male ICR mice |
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Dosage form |
Oral administration, 3 mg/kg, daily |
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Applications |
GSK1120212 was effective at blocking phosphorylation of ERK over 24 h and 7 d. To test whether the inhibitor blocked adaptive growth, mice were treated with GSK1120212 and/or the trypsin inhibitor camostat mesylate S (TI) for 7 d. TI-induced pancreatic growth was blocked by GSK1120212 as measured by pancreatic mass, protein, DNA, and RNA content. These results show that GSK1120212 like PD0325901 blocks pancreatic adaptive growth induced by TI. |
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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] Watanabe M, Sowa Y, Yogosawa M, et al. Novel MEK inhibitor trametinib and other retinoblastoma gene (RB)-reactivating agents enhance efficacy of 5‐fluorouracil on human colon cancer cells. Cancer science, 2013, 104(6): 687-693. [2] Holtz B J, Lodewyk K B, Sebolt-Leopold J S, et al. ERK Activation is Required for CCK-mediated Pancreatic Adaptive Growth in Mice. American Journal of Physiology-Gastrointestinal and Liver Physiology, 2014: ajpgi. 00163.2014. |
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| Description | Trametinib (GSK1120212) is a highly specific and potent inhibitor of MEK1/2 with IC50 of 0.92 nM/1.8 nM. | |||||
| Targets | MEK1 | MEK2 | ||||
| IC50 | 0.92 nM | 1.8 nM | ||||
Quality Control & MSDS
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