Inhibition of RET tyrosine kinase by SU5416

Article Article scientifique Article Inhibition of RET tyrosine kinase by SU5416 eng 2006-10 author Mologni Luca author Sala Elisa 983991 author Cazzaniga Sara author Rostagno Roberta author Kuoni Thomas 624737 author Puttini Miriam author Bain Jenny author Cleris Loredana author Redaelli Sara author Riva Barbara author Formelli Franca author Scapozza Leonardo 600318 author Gambacorti-Passerini Carlo 199-212 10.1677/jme.1.01999 17032739 0952-5041 https://jme.bioscientifica.com/view/journals/jme/37/2/0370199.xml <p>Thyroid neoplasia is frequently associated with rearranged during transfection (RET) proto-oncogene mutations that cause hyperactivation of RET kinase activity. Selective inhibition of RET-mediated signaling should lead to an efficacious therapy. SU5416 is a potent inhibitor of vascular endothelial cell growth factor receptor, c-Kit, and FLT-3 receptor tyrosine kinases presently used in clinical trials. We found that SU5416 inhibits RET with similar potency, both in cell-free assays and in cells, thus causing proliferation arrest in oncogenic RET-transfected cells and in papillary thyroid carcinoma (PTC) cells expressing the RET/PTC1 oncogene, but not in RET-negative control cells. SU5416 inhibited RET-mediated signaling through the extracellular signal regulated kinase (ERK) and JNK pathways. In addition, we show that a naturally occurring MEN2 mutation at codon 804 confers resistance to SU5416, but not to the related compound SU4984. We provide a possible explanation to these results by using molecular docking. Finally, SU5416 was also assessed against an array of 52 tyrosine and serine/threonine kinases.</p> Dewey 615 31 Section des sciences pharmaceutiques 17 false Journal of molecular endocrinology 37 2 1588e590-b24c-457f-b6a2-590db406ebf2 Article (Published version) Restricted 1479-6813-0370199.pdf 406261 application/pdf restrictedAccess Faculté des sciences / Section des sciences pharmaceutiques

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Inhibition of RET tyrosine kinase by SU5416	Journal of molecular endocrinology			2006	129	0

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Sala, Elisa