AG 556是一种选择性的EGFR抑制剂,IC50值为1.1 μM.

表皮生长因子受体(EGFR)是表皮生长因子的细胞表面受体,在肿瘤侵袭和癌细胞增殖中起重要作用.

AG 556是一种选择性的EGFR抑制剂.在表达KIR2.3或Kir2.1的HEK 293细胞中,AG 556(10 μM)可逆地降低KIR2.3或Kir2.1电流.另外,AG 556抑制KIR2.3或Kir2.1通道的酪氨酸磷酸化.EGF (100 ng/ml)增加KIR2.3电流,而这种作用被AG556抑制[1] [2].AG556将85％的细胞阻滞在G1 / S期并通过磷酸化Cdk2上酪氨酸15,抑制Cdk2活化[3].

在感染大肠杆菌0111: B4的犬模型中,AG 556增加存活时间.AG 556增加平均动脉压\氧气输送\心输出量\肺泡动脉氧梯度和左室射血分数,这表明AG 556提高存活率.另外,AG 556显著降低血清TNF的水平,这表明AG 556抑制细胞信号传导途径和细胞因子诱导的多器官衰竭[4].

参考文献：
[1].  Zhang DY, Zhang YH, Sun HY, et al. Epidermal growth factor receptor tyrosine kinase regulates the human inward rectifier potassium K(IR)2.3 channel, stably expressed in HEK 293 cells. Br J Pharmacol, 2011 Nov, 164(5): 1469-1478 [1].
[2].  Zhang DY, Wu W, Deng XL, et al. Genistein and tyrphostin AG556 inhibit inwardly-rectifying Kir2.1 channels expressed in HEK 293 cells via protein tyrosine kinase inhibition. Biochim Biophys Acta, 2011, 1808(8): 1993-1999.
[3].  Kleinberger-Doron N, Shelah N, Capone R, et al. Inhibition of Cdk2 activation by selected tyrphostins causes cell cycle arrest at late G1 and S phase. Exp Cell Res, 1998, 241(2): 340-351.
[4].  Sevransky JE, Shaked G, Novogrodsky A, et al. Tyrphostin AG 556 improves survival and reduces multiorgan failure in canine Escherichia coli peritonitis. J Clin Invest, 1997, 99(8): 1966-1973.