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

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

Cancer cell (2004-03-31)
Carlos García-Echeverría, Mark A Pearson, Andreas Marti, Thomas Meyer, Juergen Mestan, Johann Zimmermann, Jiaping Gao, Josef Brueggen, Hans-Georg Capraro, Robert Cozens, Dean B Evans, Doriano Fabbro, Pascal Furet, Diana Graus Porta, Janis Liebetanz, Georg Martiny-Baron, Stephan Ruetz, Francesco Hofmann
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
PhosphoDetect Anti-Insulin Receptor (pTyr1162/1163) Rabbit pAb, liquid, Calbiochem®
Sigma-Aldrich
NVP-AEW541, ≥98% (HPLC)