KRASG12D Inhibitor
MRTX1133
MRTX1133 is an investigational and selective small molecule inhibitor of KRASG12D.
MRTX1133
MRTX1133 is an investigational and selective small molecule inhibitor of KRASG12D.
Mechanism of Action
Mirati is developing investigational drug candidate, MRTX1133, which is optimized to inhibit KRASG12D and has the potential to be a first-in-class therapeutic.
In preclinical studies, MRTX1133 exhibited an ability to bind the KRASG12D protein in both active and inactive states and selectively inhibit KRASG12D mutant, but not KRAS wild-type, tumor cells.
Preclinical studies of MRTX1133 demonstrated key characteristics including:
Low nanomolar potency across multiple cellular models of KRASG12D12
Predicted ~50-hour half-life12
1,000+ fold selective for mutant KRASG12D vs wild-type KRAS12
MRTX1133 demonstrated dose-dependent inhibition of the KRAS pathway tumor regression in G12D-mutant tumor models and increased activity when combined with rational combination approaches.