For research use only. Not for therapeutic Use.
Trametiglue, a derivative of Trametinib (HY-10999), targets both KSR-MEK and RAF-MEK with unprecedented potency and selectivity via unique interfacial binding interactions[1].
Trametiglue retains the strong binding potency and residence time of Trametinib on KSR-bound MEK[1].
Trametiglue, unlike Trametinib but similar to Avutometinib (HY-18652), enhances interactions between endogenous BRAF and MEK1[1].
Trametiglue (1 μM) demonstrates high selectivity towards MEK1 and MEK2 in direct binding assays. Trametiglue also displays high selectivity in a panel of active kinases measured for inhibition of MEK1 and MEK2 substrate phosphorylation or direct MEK1 phosphorylation by the upstream kinases[1].
Trametiglue (5 days) inhibits HCT116, A375, A549 and SK-MEL-239 cells viability with IC50s of 0.07, 0.07, 0.12 and 0.47 nM, respectively[1].
Trametiglue (10 nM; 10 days) inhibits colony formation in KRAS-mutant and BRAF-mutant cancer cell lines with higher potency than Trametinib[1].
| Catalog Number | I041301 |
| CAS Number | 2666940-97-0 |
| Synonyms | 3-cyclopropyl-5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-1-[3-(methylsulfamoylamino)phenyl]pyrido[4,3-d]pyrimidine-2,4,7-trione |
| Molecular Formula | C25H24FIN6O5S |
| Purity | ≥95% |
| InChI | InChI=1S/C25H24FIN6O5S/c1-13-21-20(22(31(3)23(13)34)29-19-10-7-14(27)11-18(19)26)24(35)33(16-8-9-16)25(36)32(21)17-6-4-5-15(12-17)30-39(37,38)28-2/h4-7,10-12,16,28-30H,8-9H2,1-3H3 |
| InChIKey | DNNMBAWCLGMMRJ-UHFFFAOYSA-N |
| 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)NS(=O)(=O)NC)C5CC5 |
| Reference | [1]. Khan ZM, et al. Structural basis for the action of the drug trametinib at KSR-bound MEK. Nature. 2020 Dec;588(7838):509-514. |
