HRX-0233 (HRX0233) is a potent, selective MAP2K4 (MKK4) inhibitor, HRX-0233 is synergistic with RAS inhibitors in KRAS-mutant cancers.
Combination of sotorasib, a drug targeting KRASG12C, and the MAP2K4 inhibitor HRX-0233 prevents this feedback activation and is highly synergistic in a panel of KRASG12C-mutant lung and colon cancer cells.
Combining HRX-0233 and sotorasib is well-tolerated and resulted in durable tumor shrinkage in mouse xenografts of human lung cancer cells.
HRX-0233 combined with MEK inhibition suppresses tumor growth without toxicity in a H2122 xenograft model.
