Selumetinib又称为AZD6244、司美替尼、Y-142886，是一种高效、非ATP竞争性MEK1抑制剂，IC50为14 nM。在多种癌细胞中，Selumetinib抑制基底和诱导的ERK1/2磷酸化水平，IC50为8 nM。作用于HCC细胞，Selumetinib引起生长抑制、提高切割后caspase-3、caspase-7和聚ADP核糖聚合酶，并抑制ERK1/2和p90RSK磷酸化水平，抑制HCC细胞生长。在多种肿瘤模型中，Selumetinib也具有明显的效力，显著抑制ERK活性，抑制肿瘤生长，并抑制肺转移。

参考文献

[1] Yeh TC, et al. Biological characterization of ARRY-142886 (AZD6244), a potent, highly selective mitogen-activated protein kinase kinase 1/2 inhibitor. Clin. Cancer Res. 13: 1576-1583 (2007).

[2] Huynh H, et al. Targeted inhibition of the extracellular signal-regulated kinase kinase pathway with AZD6244 (ARRY-142886) in the treatment of hepatocellular carcinoma. Mol. Cancer Ther. 6: 138-146 (2007).

[3] Ball DW, et al. Selective growth inhibition in BRAF mutant thyroid cancer by the mitogen-activated protein kinase kinase 1/2 inhibitor AZD6244. J. Clin. Endocrinol. Metab. 92: 4712-4718 (2007).

[4] Chang Q, et al. Effects of combined inhibition of MEK and mTOR on downstream signaling and tumor growth in pancreatic cancer xenograft models. Cancer Biol. Ther. 8: 1893-1901 (2009).

[5] Meng J, et al. Combination treatment with MEK and AKT inhibitors is more effective than each drug alone in human non-small cell lung cancer in vitro and in vivo. PLoS One 5: e14124 (2010).

[6] Garon EB, et al. Identification of common predictive markers of in vitro response to the Mek inhibitor selumetinib (AZD6244; ARRY-142886) in human breast cancer and non-small cell lung cancer cell lines. Mol Cancer Thera, 9 (7): 1985-1994 (2010).

[7] Grasso S, et al. Resistance to Selumetinib (AZD6244) in Colorectal Cancer Cell Lines is Mediated by p70S6K and RPS6 Activation. Neoplasia16(10): 845–860 (2014).

[8] Bartholomeusz C, et al. MEK Inhibitor Selumetinib (AZD6244; ARRY-142886) Prevents Lung Metastasis in a Triple-Negative Breast Cancer Xenograft Model. Cancer Ther 14(12): 2773–2781 (2015).

冰袋运输。粉末直接保存于-20 ºC，有效期2年。建议分装后-20ºC避光保存，避免反复冻存，至少可存放6个月。