MRTX-1257 is a selective, irreversible, and covalent inhibitor of KRAS G12C. It has an IC50 of 900 pM for KRAS dependent ERK phosphorylation in H358 cells. MRTX1257 demonstrated 31% bioavailability in the mouse, with free fraction exposures well above the cellular potency In a PK/PD experiment, 77% target engagement.

MRTX-1257在3、10、30以及100 mg/kg剂量组显示持续的肿瘤退缩。以100 mg/kg的剂量每日给药可引起完全反应，在停药后70天以上仍维持该反应。在小鼠MIA PaCa-2 G12C移植模型中，MRTX-1257（1 mg/kg、3 mg/kg、10 mg/kg、30 mg/kg及100 mg/kg，口服，每日一次，连续30天）在所有剂量组均迅速抑制肿瘤生长。