MRTX-1257 是选择性的、可口服的不可逆共价KRas G12C抑制剂，其在 H358 细胞中测得 KRas 依赖 ERK 磷酸化的IC50值为 900 pM。

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 shows sustained regression at 3,10, 30, and 100 mg/kg dose groups. MRTX-1257 dosed of 100 mg/kg daily causes complete responses that are maintained >70 days after cessation of treatment. MRTX-1257 (1 mg/kg, 3 mg/kg, 10 mg/kg, 30 mg/kg and 100 mg/kg, orally, daily for 30 days) displays rapid tumor growth inhibition at all dose groups in MIA PaCa-2 G12C Xenograft model in mice .

2206736-04-9

C33H39N7O2

565.71

DMSO:54 mg/mL(95.46 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years