In vivo antitumor activity of NVP-AEW541-A novel, potent, and selective inhibitor of the IGF-IR kinase.

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阅读量：

148

作者：

C Garc??A-Echeverr??A，MA Pearson，A Marti，T Meyer，J Mestan，J Zimmermann，J Gao，J Brueggen，HG Capraro，R Cozens

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摘要：

IGF-IR-mediated signaling promotes survival, anchorage-independent growth, and oncogenic transformation, as well as tumor growth and metastasis formation in vivo. NVP-AEW541 is a pyrrolo[2,3-]pyrimidine derivative small molecular weight kinase inhibitor of the IGF-IR, capable of distinguishing between the IGF-IR (IC = 0.086 μM) and the closely related InsR (IC = 2.3 μM) in cells. As expected for a specific IGF-IR kinase inhibitor, NVP-AEW541 abrogates IGF-I-mediated survival and colony formation in soft agar at concentrations that are consistent with inhibition of IGF-IR autophosphorylation. In vivo, this orally bioavailable compound inhibits IGF-IR signaling in tumor xenografts and significantly reduces the growth of IGF-IR-driven fibrosarcomas. Thus, NVP-AEW541 represents a class of selective, small molecule IGF-IR kinase inhibitors with proven in vivo antitumor activity and potential therapeutic application.

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关键词：

Insulin-Like Growth Factor I Nevirapine Phosphotransferases in vivo 胰岛素样生长因子Ⅰ 奈韦拉平磷酸转移酶类

DOI：

10.1016/S1535-6108(04)00051-0

被引量：

1833

年份：

2004