2x2k

Crystal Structure of phosphorylated RET tyrosine kinase domain with inhibitor

spinqualitylabelsall models 2x2k, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2x2k is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: FMT, X2K NonStd Res: PTR Related: 2ivu, 2ivt, 2ivs, 2ivv, 2x2m, 2x2l Activity: Receptor protein-tyrosine kinase, with EC number 2.7.10.1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The synthesis, structure-activity relationships (SAR) and structural data of a series of indolin-2-one inhibitors of RET tyrosine kinase are described. These compounds were designed to explore the available space around the indolinone scaffold within RET active site. Several substitutions at different positions were tested and biochemical data were used to draw a molecular model of steric and electrostatic interactions, which can be applied to design more potent and selective RET inhibitors. The crystal structures of RET kinase domain in complex with three inhibitors were solved. All three compounds bound in the ATP pocket and formed two hydrogen bonds with the kinase hinge region. Crystallographic analysis confirmed predictions from molecular modelling and helped refine SAR results. These data provide important information for the development of indolinone inhibitors for the treatment of RET-driven cancers. Synthesis, structure-activity relationship and crystallographic studies of 3-substituted indolin-2-one RET inhibitors.,Mologni L, Rostagno R, Brussolo S, Knowles PP, Kjaer S, Murray-Rust J, Rosso E, Zambon A, Scapozza L, McDonald NQ, Lucchini V, Gambacorti-Passerini C Bioorg Med Chem. 2010 Feb 15;18(4):1482-96. Epub 2010 Jan 11. PMID:20117004 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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