MRTX1133

MRTX1133 is a small molecule, noncovalent, and highly selective inhibitor of the KRAS G12D mutant protein. Developed through structure-based drug design by Mirati Therapeutics, it binds to the switch II pocket of KRAS G12D and blocks its activity by preventing SOS1-catalyzed nucleotide exchange and formation of the KRAS G12D/GTP/RAF1 complex. This inhibition disrupts downstream signaling pathways essential for tumor cell proliferation and survival in cancers driven by this mutation. Preclinical studies have demonstrated potent antitumor efficacy both in vitro and in vivo, particularly against pancreatic ductal adenocarcinoma (PDAC) models harboring KRAS G12D mutations. MRTX1133 is currently being evaluated in phase 1/2 clinical trials for advanced solid tumors with this mutation[1][2][5][6].

Other names

4-[4-(3,8-Diazabicyclo[3.2.1]oct-3-yl)-8-fluoro-2-[[(2R,7aS)-2-fluorotetrahydro-1H-pyrrolizin-7a(5H)-yl]methoxy]pyrido[4,3-d]pyrimidin-7-yl]-5-ethynyl-6-fluoro-2-naphthalenol