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

Garcia-Echeverria, Carlos and Pearson, Mark Andrew and Marti, Andreas and Meyer, Thomas and Mestan, Juergen and Zimmermann, Johann and Gao, Jiaping and Brueggen, Josef and Capraro, Hans-Georg and Cozens, Robert and Evans, Dean Brent and Fabbro, Doriano and Furet, Pascal and Porta, Diana Graus and Liebetanz, Janis and Martiny-Baron, Georg and Ruetz, Stephan and Hofmann, Francesco (2004) In vivo antitumor activity of NVP-AEW541-A novel, potent, and selective inhibitor of the IGF-IR kinase. Cancer Cell, 5 (3). pp. 231-239. ISSN 1535-6108

Abstract

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-d]pyrimidine derivative small molecular weight kinase inhibitor of the IGF-IR, capable of distinguishing between the IGF-IR (IC50 = 0.086 microM) and the closely related InsR (IC50 = 2.3 microM) 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.

Item Type: Article
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Additional Information: author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used
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Date Deposited: 14 Dec 2009 13:54
Last Modified: 31 Jan 2013 01:07
URI: https://oak.novartis.com/id/eprint/766

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