MRTX1133

CAS NO.:2621928-55-8

Molecular Formula:C₃₃H₃₁F₃N₆O₂

Molecular Weight:600.63

Purity: > 98%

Solubility (R.T.: 25℃): DMSO

Stability: - 20℃ 2 years

MRTX1133 is a noncovalent, potent, and selective KRAS G12D inhibitor. MRTX1133 optimally fills the switch II pocket and extends three substituents to favorably interact with the protein, resulting in an estimated KD against KRAS G12D of 0.2 pM. MRTX1133 prevents SOS1-catalyzed nucleotide exchange and/or formation of the KRAS G12D/GTP/RAF1 complex, thereby inhibiting mutant KRAS-dependent signal transduction. MRTX1133 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.

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