BI-2852 is a potent inhibitor for in vitro use that directly targets GTP-bound KRAS, which is the major form present in cancer cells carrying KRAS mutations. MRTX1133 is a noncovalent, potent, and selective KRAS G12D inhibitor which optimally fills the switch II pocket and extends three substituents to favorably interact with the protein. It selectively inhibits KRAS G12D mutant, but not KRAS wild-type, tumor cells. MRTX1133 has single digit nanomolar activity in cellular assays and marked in vivo efficacy in tumor models harboring KRAS G12D mutations.

protein – small molecule | biotinylated target | competition assay | thermodynamics | van’t Hoff analysis | enthalpy | entropy | MOX-P-118