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:

Potent

Low nanomolar potency across multiple cellular models of KRASG12D12

Long half-life

Predicted ~50-hour half-life12

Highly selective

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.