APS-2-79

2002381-25-9

C23H21N3O3

DMSO : >= 33 mg/mL (85.18 mM)

MAPK/ERK Pathway

APS-2-79 behaves as a kinase suppressor of Ras (KSR)-dependent antagonist of RAF-mediated MEK phosphorylation. APS-2-79 binds directly to KSR2 within the KSR2-MEK1 complex with an IC ₅₀ of 120+/-23 nM for KSR2. IC50 & Target: IC50: 120+/-23 nM (KSR2)^[1] In Vitro: APS-2-79 (1 uM) shifts the cell viability dose response to Trametinib in Ras-mutant cell lines HCT-116 and A549, but not BRAF mutant cell lines SK-MEL-239 and A375. Although the cellular effects of APS-2-79 alone are modest, combination analysis over full concentration matrices reveal that kinase suppressor of Ras (KSR)-inactive state (KSRi) synergizes with Trametinib, and other MEK inhibitors, specifically in KRAS mutant cell lines. APS-3-77, and additional control compounds, do not demonstrate Ras-mutant-specific synergy, supporting the hypothesis that the enhanced activity of Trametinib when combined with APS-2-79 depends on co-modulation of KSR^[1].