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A single amino acid exchange inverts susceptibility of related receptor tyrosine kinases for the ATP-site inhibitor STI-571

Böhmer, F. D. ; Karagyozov, L. ; Uecker, A. ; Serve, H. ; Botzki, A. ; Mahboobi, Siavosh ; Dove, Stefan



Abstract

The tyrosine kinase inhibitor STI-571 potently blocks BCR-Abl, platelet-derived growth factor (PDGF) a- and b-receptors, and c-Kit kinase activity. However Flt3, a receptor tyrosine kinase closely related to PDGF receptors and c-Kit, is not inhibited by STI-571. Sequence alignments of different kinases and indications from the crystal structure of the STI-571 Abl kinase complex revealed amino ...

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