MRTX-0902

MRTX-0902 is an inhibitor of the protein-protein interaction between son of sevenless homolog 1 (SOS1) and K-Ras containing a glycine-to-cysteine mutation at position 12 (K-Ras^G12C; K_i = 1.9 nM).¹ It is selective for the SOS1-K-Ras^G12C protein-protein interaction over the SOS1 and wild-type K-Ras protein-protein interaction (IC₅₀ = >10,000 nM). MRTX-0902 decreases phosphorylated ERK levels in MKN1 gastric adenosquamous carcinoma cells (IC₅₀ = 29 nM). In vivo, MRTX-0902 (25 or 50 mg/kg twice per day), in combination with the covalent inhibitor of K-Ras^G12C MTX-849 (Item No. 31440), reduces tumor volume and phosphorylated ERK levels in a PaCa-2 pancreatic cancer mouse xenograft model.

WARNING This product is not for human or veterinary use.

1. Ketcham, J.M., Haling, J., Khare, S., et al. Design and discovery of MRTX0902, a potent, selective, brain-penetrant, and orally bioavailable inhibitor of the SOS1:KRAS protein-protein interaction. J. Med. Chem. 65(14), 9678-9690 (2022).