MRTX-1133 (MRTX1133) is a potent, selective and noncovalent inhibitor KRAS G12D with SPR Kd of 0.2 nM, AlphaLISA IC50 of 5 nM.
MRTX1133 inhibited ERK phosphorylation in the AGS cell line with an IC50 of 2 nM, demonstrated high potency against AGS cell line in a 2D viability assay with IC50 of 6 nM, >500-fold selectivity against MKN1, a cell line which is dependent on wild-typ KRAS.
MRTX1133 modulated KRAS-dependent ERK phosphorylation in the Panc 04.03 xenograft tumor model at 30 mg/kg BID (IP), MRTX1133 exhibted dose-dependent antitumor activity with 94% growth inhibition observed at 3 mg/kg BID (IP) and tumor regressions of -62% and -73% observed at 10 and 30 mg/kg BID (IP), respectively, no significant antitumor activity in the non-KRASG12D tumor model MKN1.
