SGX-523

SGX-523是肝细胞生长因子受体(Met)的一个新型的、有效的、ATP-竞争性并高度选择性抑制剂，IC50值为4 nM[1]。

SGX-523在胃癌细胞株GTL16（IC50值40 nM）和人类肺癌细胞株A549（IC50值12 nM）中抑制Met自身磷酸化[1]。此外，在口服填喂SGX-523的移植瘤型鼠派生的癌细胞系GTL16和人类GBM细胞系U87MG中观察到肿瘤退缩[1]。

SGX523已表现出抑制大脑癌细胞系（包括U87、U373、DAOY和神经胶质瘤干细胞1228）中MEK、MAPK和Akt的磷酸化。大脑的癌细胞和干细胞中MEK的抑制导致细胞增殖、细胞周期G1/S进程、细胞迁移和细胞入侵[2]。

参考文献：
[1] Buchanan SG1, Hendle J, Lee PS, Smith CR, Bounaud PY, Jessen KA, Tang CM, Huser NH, Felce JD, Froning KJ, Peterman MC, Aubol BE, Gessert SF,Sauder JM, Schwinn KD, Russell M, Rooney IA, Adams J, Leon BC, Do TH, Blaney JM, Sprengeler PA, Thompson DA, Smyth L, Pelletier LA, Atwell S, Holme K,Wasserman SR, Emtage S, Burley SK, Reich SH.  SGX523 is an exquisitely selective, ATP-competitive inhibitor of the MET receptor tyrosine kinase with antitumor activity in vivo. Mol Cancer Ther. 2009 Dec;8(12):3181-90.
[2] Guessous F1, Zhang Y, diPierro C, Marcinkiewicz L, Sarkaria J, Schiff D, Buchanan S, Abounader R. An orally bioavailable c-Met kinase inhibitor potently inhibits brain tumor malignancy and growth. Anticancer Agents Med Chem. 2010 Jan;10(1):28-35.