BAY-293 (BAY293, BAY 293) is a potent, cell-active SOS1 inhibitor that disrupts the KRAS-SOS1 interaction with IC50 of 21 nM.
BAY-293 displays no significant activity against KRAS WT-CRAF RBD, CDC42 and EGFR (>20 uM).
BAY-293 blocks reloading of KRAS with GTP, does not stabilize KRASWT or KRASG12C.
BAY-293 inhibits the activation of RAS in HeLa cells with IC50 of 410 nM, efficiently inhibits pERK levels in K562 cells after incubation for 60 min without affecting total protein levels of ERK (IC50=180 nM).
BAY-293 shows antiproliferative activity against wild-type KRAS cell lines (K562, MOLM-13; IC50~1 uM) and cell lines with KRASG12C mutation (NCI-H358, Calu-; IC50~3 uM) by preventing formation of the KRAS-SOS1 complex, also shows synergic antiproliferative effect with covalent KRASG12C inhibitor ARS-853.
BAY-293 is a valuable chemical probe for investigation of the activation of KRAS by SOS1.