WM-S1-030 is a highly potent, specific inhibitor of recepteur d'origine nantais (RON kinase, MST1R) with IC50 of 0.39 nM in in vitro enzyme activity.
WM-S1-030 inhibits the activity of Met family members and a few tyrosine kinases (TKs) (Axl, Flt4, Mer, and TRKC), with IC50 values < 10 nM.
WM-S1-030 is >100-fold selective for the TKs DDR2, Flt3, IGF1R, and ROS, and >1000-fold selective for all other kinases against a panel of kinases, except Fms, KDR and TrkA.
WM-S1-030 shows strong potency against colo320HSR cells, with IC50 values of 27.41 nM, 98.7 nM, and 137.2 nM, in cell lines expressing RONΔ160, RONΔ155, and RONΔ165, respectively, which is much more potent than BMS777607.
WM-S1-030 effectively inhibits the RON variants and exerts potent anticancer efficacy in RON variant-positive colon cancer.
WM-S1-030 elicits notable antitumor immunity in anti-PD-1 resistant cell derived mouse model.