AMG-510 是一种可口服的选择性KRas G12C共价抑制剂，可将 KRas G12C 锁定在非活跃的 GDP 约束状态，能使 KRas G12C 肿瘤消退。

AMG-510 is a selective and orally bioavailable KRAS G12C covalent inhibitor.

In cellular assays, AMG 510 covalently modified KRASG12C and inhibited KRASG12C signaling as measured by phosphorylation of ERK1/2 (p-ERK) in all KRAS p.G12C-mutant cell lines tested but did not inhibit p-ERK in cell lines with various other KRAS mutations.?AMG 510 also selectively impaired viability of KRAS p.G12C mutant cell lines but did not affect cell lines with other KRAS mutations[1].

In vivo pharmacodynamic assays demonstrated dose- and time-dependent inhibition of KRASG12Csignaling in human pancreatic and NSCLC tumor xenografts.?Covalent modification of KRASG12C by AMG 510 was measured by mass spectrometry and correlated with p-ERK inhibition in tumors.?AMG 510 significantly inhibited the growth of KRAS p.G12C xenografts and resulted in tumor regression.?Combination treatment of AMG 510 with standard-of-care and targeted agents demonstrated enhanced tumor growth inhibition compared to either single agent.?In a syngeneic model of KRAS p.G12C mutant cancer, AMG 510 treatment significantly inhibited tumor growth and caused regression[1].

2296729-00-3

C30H30F2N6O3

560.59

AMG-510

DMSO:50 mg/mL (89.19 mM),Need ultrasonic
H2O:33.33 mg/mL (59.46 mM),ultrasonic and adjust pH to 11 with NaOH
Powder: -20°C for 3 years
In solvent: -80°C for 2 years