TAE226(NVP-TAE226) is a potent ATP-competitive inhibitor that inhibits a variety of tyrosine protein kinases, especially FAK and IGF-IR kinases, with IC50 values of 5.5nM and 140nM, respectively. TAE226 antagonizes both FAK and IGF-IR signaling pathways, resulting in growth inhibition, cell cycle arrest, attenuation of tumor invasion, and induction of apoptosis. TAE226 also effectively inhibits Pyk2 and the insulin receptor (InsR), with IC50 values of 3.5nM and 44nM, respectively[1][2].
In vitro, treatment with 1 and 10μM TAE226 for 1–5 days inhibited the growth of U87, U87/EGFR, and U87/EGFRvIII cell lines in a dose-dependent manner, with U87/EGFR and U87/EGFRvIII cells showing greater sensitivity to TAE226[1].
In vivo, oral administration of TAE226 (50 or 75mg/kg) once daily for 5 days followed by 2 days off for 4 weeks extended the median survival of U87 xenograft animals by 6 and 7 days, respectively[1]. Oral administration of TAE226 (50 or 75mg/kg) once daily for 5 days followed by 2 days off for 4 weeks extended the median survival of LN229 xenograft animals by 19 and 25 days[1].
References:
[1] Liu TJ, LaFortune T, Honda T, et al. Inhibition of both focal adhesion kinase and insulin-like growth factor-I receptor kinase suppresses glioma proliferation in vitro and in vivo. Mol Cancer Ther. 2007;6(4):1357-1367.
[2] Delimont D, et al. Laminin α2-mediated focal adhesion kinase activation triggers Alport glomerular pathogenesis. PLoS One. 2014 Jun 10;9(6):e99083.
TAE226(NVP-TAE226)是一种强效的ATP竞争性抑制剂，能抑制多种酪氨酸蛋白激酶，尤其是FAK和IGF-IR激酶，其IC50值分别为5.5nM和140nM。TAE226能够阻断FAK和IGF-IR信号通路，从而实现生长抑制、细胞周期停滞、肿瘤侵袭减弱以及细胞凋亡诱导的效果。TAE226还能够有效抑制Pyk2和胰岛素受体（InsR），其IC50值分别为3.5nM和44nM[1][2]。
体外实验中，用1和10μM的TAE226处理1–5天，可剂量依赖性地抑制U87、U87/EGFR和U87/EGFRvIII细胞系的生长，其中U87/EGFR和U87/EGFRvIII细胞对TAE226更为敏感[1]。
体内实验中，口服给予TAE226（50或75mg/kg），每日一次，连续给药5天后停药2天，按此周期持续4周，可使U87移植瘤动物的中位生存期分别延长6天和7天[1]。同样的给药方案下，口服给予TAE226（50或75mg/kg），每日一次，连续给药5天后停药2天，持续4周，可使LN229移植瘤动物的中位生存期分别延长19天和25天[1]。