Trametinib (GSK1120212) is an orally-available, tetrahydropyridopyrimidine-based, allosteric inhibitor of MEK1 and MEK2, with an IC50 of 1.6 and 3.4 nM when using B-Raf as its activator. [1] It is highly selective over broad inhibitory panel of 98 kinases at 10 uM. In vitro, Trametinib strongly inhibits human colorectal cancer cell lines known to have a constitutively active B-Raf or Ras mutation; in particular, IC50 inhibition values of HT-29, COLO205, HCT116, LS-174T, and SW620 are 0.48, 0.52, 5.7, 4.1, and 2.3 nM, respectively. [1]
Trametinib prevents Raf-dependent MEK phosphorylation (S217 for MEK1), resulting in prolonged p-Erk1/2 inhibition. [2] In a broad panel of cancer cell lines, Trametinib was shown to inhibit the MEK1/2-dependent activating dual phosphorylation of ERK1/2 on both T202 and Y204.
Trametinib has been shown to work in combination with other B-Raf inhibitors, overcoming resistant lines mediated by NRAS or MEK mutations. [3]
Technical information:
| Chemical Formula: | C26H23FIN5O4 | |
| CAS #: | 871700-17-3 | |
| Molecular Weight: | 615.39 | |
| Purity: | > 98% | |
| Appearance: | White | |
| Chemical Name: | N-(3-(3-cyclopropyl-5-(2-fluoro-4-iodophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenyl)acetamide | |
| Solubility: | Up to 10 mM in DMSO | |
| Synonyms: | GSK-1120212, GSK1120212, JTP-74057, Trametinib |
Shipping Condition: The product is shipped in a glass vial at ambient temperature.
Storage condition: For longer shelf life, store solid powder at 4oC desiccated, or store DMSO solution at -20oC.
Reference:
| 1. | Yamaguchi et al., Antitumor activities of JTP-74057 (GSK1120212), a novel MEK1/2 inhibitor, on colorectal cancer cell lines in vitro and in vivo. Int. J. Oncol. 2011, 39(1), 23-31. Pubmed ID: 21523318 |
| 2. | Gilmartin et al., GSK1120212 (JTP-74057) is an inhibitor of MEK activity and activation with favorable pharmacokinetic properties for sustained in vivo pathway inhibition. Clin. Cancer Res. 2011, 17, 989-1000. Pubmed ID: 21245089 |
| 3. | Greger et al., Combinations of BRAF, MEK, and PI3K/mTOR inhibitors overcome acquired resistance to the BRAF inhibitor GSK2118436 dabrafenib, mediated by NRAS or MEK mutations. Mol. Cancer Ther. 2012, 11(4), 909-920. Pubmed ID: 22389471 |
Other Information:
Product Specification (pdf)
MSDS (pdf)
Certificate of Analysis is available upon request.
