SotorasibSotorasib
MedChemExpress (MCE)
HY-114277
2296729-00-3
AMG-510
99.94%
-20°C, stored under nitrogen *In solvent : -80°C, 6 months
-20°C, 1 month (stored under nitrogen)
Room temperature in continental US
may vary elsewhere.
Sotorasib (AMG-510) is a first-in-class, orally bioavailable, and selective KRAS G12C covalent inhibitor. Sotorasib irreversibly inhibits KRAS G12C by locking it in an inactive GDP-bound state. Sotorasib is the first KRAS G12C inhibitor in clinical development and leads to the regression of KRAS G12C tumors.
In cellular assays, Sotorasib (AMG-510) covalently modifies KRAS G12C and inhibits KRAS G12C signaling as measured by phosphorylation of ERK1/2 (p-ERK) in all KRAS p.G12C-mutant cell lines[2].?Sotorasib (AMG-510
1-10 μM
72 hours) also potently impairs cellular viability in both NCI-H358 and MIA PaCa-2 with IC50≈0.006 μM and 0.009 μM, respectively. Non-KRASG12C lines are insensitive to Sotorasib (IC50>7.5 μM)[3].
In preclinical tumor models, Sotorasib (AMG-510) rapidly and irreversibly binds to KRAS G12C, providing durable suppression of the mitogen-activated protein kinase (MAPK) signaling pathway. Sotorasib (orally
once daily) is capable of inducing tumor regression in mouse models of KRAS G12C cancer[3].
KRAS(G12C)
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[1]. Marwan Fakih, et al, Phase 1 study evaluating the safety, tolerability, pharmacokinetics (PK), and efficacy of AMG 510, a novel small molecule KRASG12Cinhibitor, in advanced solid tumors. Journal of Clinical Oncology.
[2]. Karen Rex, et al. Abstract 3090: In vivo characterization of AMG 510 - a potent and selective KRASG12Ccovalent small molecule inhibitor in preclinical KRASG12Ccancer models. Experimental and Molecular Therapeutics.
[3]. Canon J, et al. The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity. Nature. 2019 Nov
575(7781):217-223. [Content Brief]
[4]. Brian A. Lanman, et al.Abstract 4455: Discovery of AMG 510, a first-in-human covalent inhibitor of KRASG12C for the treatment of solid tumors. Cancer Chemistry.