AEE788 (NVP-AEE788)

AEE788（CAS号 497839-62-0）是EGFR和HER2的有效抑制剂，IC50值分别为2 nM和6 nM。

表皮生长因子受体（EGFR）是一种细胞表面受体酪氨酸激酶。受体活化导致二聚化和酪氨酸自磷酸化。它诱导一系列下游细胞应答级联反应，如基因表达修饰、细胞增殖和细胞骨架重排等。

在HCT 15结肠癌细胞中，AEE788增强塞来昔布（celecoxib）介导的增殖和血管生成的阻断[1]。在EGFR和HER2过表达的各种细胞系中，AEE788表现出抗增殖活性[3]。AEE788还抑制细胞增殖，IC50 为1.7-3.8 μM，抑制表皮生长因子和体外神经调节蛋白诱导的HER1、HER2和HER3的活化[5]。

与对照小鼠相比，AEE788治疗21天后，抑制54％的肿瘤生长[2]。在ZR75.1 A3异种移植小鼠中，与单独来曲唑治疗相比，来曲唑与AEE788结合使用显著抑制肿瘤生长[4]。

参考文献：
[1] Venkatesan P, Bhutia SK, Singh AK et al.  AEE788 potentiates celecoxib-induced growth inhibition and apoptosis in human colon cancer cells. Life Sci. 2012 Oct 22;91(15-16):789-99.
[2] Park YW, Younes MN, Jasser SA et al.  AEE788, a dual tyrosine kinase receptor inhibitor, induces endothelial cell apoptosis in human cutaneous squamous cell carcinoma xenografts in nude mice. Clin Cancer Res. 2005 Mar 1;11(5):1963-73.
[3] Traxler P, Allegrini PR, Brandt R et al.  AEE788: a dual family epidermal growth factor receptor/ErbB2 and vascular endothelial growth factor receptor tyrosine kinase inhibitor with antitumor and antiangiogenic activity. Cancer Res. 2004 Jul 15;64(14):4931-41.
[4] Evans AH, Pancholi S, Farmer I et al.  EGFR/HER2 inhibitor AEE788 increases ER-mediated transcription in HER2/ER-positive breast cancer cells but functions synergistically with endocrine therapy. Br J Cancer. 2010 Apr 13;102(8):1235-43.
[5] Meco D, Servidei T, Zannoni GF et al.  Dual Inhibitor AEE788 Reduces Tumor Growth in Preclinical Models of Medulloblastoma. Transl Oncol. 2010 Oct 1;3(5):326-35.