Trametiglue is a trametinib analog that inhibits both KSR- and RAF-bound MEK and limits adaptive resistance seen with trametinib via enhanced interfacial binding. Displays significantly enhanced inhibition of RAS/ERK signaling versus trametinib is various cell lines with mutant KRAS and BRAF: IC50s/cell line - SK-MEL-239/0.47 nM, HCT116/0.07 nM, A549/0.12 nM, A375/0.07 nM. A molecular glue that is strongly selective towards MEK with no direct interaction with BRAF or CRAF.
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