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.