In vivo antitumor activity of NVP-AEW541-A novel, potent, and selective inhibitor of the IGF-IR kinase.
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Garcia-Echeverria, Carlos, Pearson, Mark Andrew, Marti, Andreas, Meyer, Thomas, Mestan, Juergen, Zimmermann, Johann, Gao, Jiaping, Brueggen, Josef, Capraro, Hans-Georg, Cozens, Robert, Evans, Dean Brent, Fabbro, Doriano, Furet, Pascal, Porta, Diana Graus, Liebetanz, Janis, Martiny-Baron, Georg, 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.
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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 |