• 生物活性

靶点及简介 ：Sotorasib (AMG-510) 是一种有效的，口服生物可利用的，选择性的 KRAS G12C 共价抑制剂。Sotorasib 将 KRAS G12C 锁定在非活跃的 GDP 约束状态。Sotorasib 是临床开发的第一个 KRAS G12C 抑制剂，能使 KRAS G12C 肿瘤消退。

AMG-510外消旋物是AMB-510的外消旋混合物，AMB-510是有效的KRAS G12C共价抑制剂。 AMG-510在DNA，RNA或蛋白质水平上选择性靶向KRAS p.G12C突变体，并通过尚未阐明的方式阻止通过KRAS p.G12C突变体的表达和/或肿瘤细胞信号传导。 这可能会抑制表达KRAS p.G12C的肿瘤细胞的生长。

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[1][2].

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].

[1] Shannon S Zhang, et al. Spotlight on Sotorasib (AMG 510) for KRAS G12C Positive Non-Small Cell Lung Cancer

[2] David S Hong, et al. KRAS G12C Inhibition with Sotorasib in Advanced Solid Tumors

[3] No authors listed. Cancer Discov. AMG 510 Shows Activity beyond NSCLC

[4] Brian A Lanman, et al. Discovery of a Covalent Inhibitor of KRAS G12C (AMG 510) for the Treatment of Solid Tumors

[5] Jude Canon, et al. The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity

• 溶解度及制备方案

• DMSO	50 mg/mL (89.19 mM)
  Water	Insoluble
  Ethanol	Insoluble

  
  

  Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
  1 mM	1.78 mL	8.92 mL	17.84 mL
  5 mM	0.36 mL	1.78 mL	3.57 mL
  10 mM	0.18 mL	0.89 mL	1.78 mL
  50 mM	0.04 mL	0.18 mL	0.36 mL

  
  

  
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