APS-2-79 is an antagonist of MEK phosphorylation by RAF through direct binding of the KSR active site.
APS-2-79 inhibits BRAF and CRAF phosphorylation of MEK in a KSR-dependent manner. APS-2-79 does not affect BRAF(V600E)-induced MAPK activation in cells. APS-2-79 impedes KSR-stimulated MAPK signalling within cells through wild-type and MEK(AAAA) equally. APS-2-79 synergizes with trametinib specifically in Ras-mutant cells compared to the HER-family and SRC-family inhibitors lapatinib and sarcatinib. APS-2-79 increases the potency of several MEK inhibitors specifically within Ras-mutant cell lines by antagonizing release of negative feedback signalling, demonstrating the potential of targeting KSR to improve the efficacy of current MAPK inhibitors. The IC50 value of APS-2-79 against ATPbiotin probe-labelling of KSR2 is 120 nM.