4aw5

Complex of the EphB4 kinase domain with an oxindole inhibitor

spinqualitylabelsall models 4aw5, resolution 2.33Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4aw5 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: 30K Related: 2bba, 2vwu, 2vwv, 2vww, 2vwx, 2vwy, 2vwz, 2vx0, 2vx1, 2x9f, 2xvd Activity: Receptor protein-tyrosine kinase, with EC number 2.7.10.1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [EPHB4_HUMAN] Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Together with its cognate ligand/functional ligand EFNB2 plays a central role in heart morphogenesis and angiogenesis through regulation of cell adhesion and cell migration. EPHB4-mediated forward signaling controls cellular repulsion and segregation form EFNB2-expressing cells. Plays also a role in postnatal blood vessel remodeling, morphogenesis and permeability and is thus important in the context of tumor angiogenesis. Publication Abstract from PubMed Variously substituted indolin-2-ones were synthesized and evaluated for activity against KDR, Flt-1, FGFR-1 and PDGFR. Extension at the 5-position of the oxindole ring with ethyl piperidine (compound 7i) proved to be the most beneficial for attaining both biochemical and cellular potencies. Further optimization of 7i to balance biochemical and cellular potencies with favorable ADME/ PK properties led to the identification of 8h, a compound with a clean CYP profile, acceptable pharmacokinetic and toxicity profiles, and robust efficacy in multiple xenograft tumor models. The design, synthesis, and biological evaluation of potent receptor tyrosine kinase inhibitors.,Kim MH, Tsuhako AL, Co EW, Aftab DT, Bentzien F, Chen J, Cheng W, Engst S, Goon L, Klein RR, Le DT, Mac M, Parks JJ, Qian F, Rodriquez M, Stout TJ, Till JH, Won KA, Wu X, Michael Yakes F, Yu P, Zhang W, Zhao Y, Lamb P, Nuss JM, Xu W Bioorg Med Chem Lett. 2012 Aug 1;22(15):4979-85. Epub 2012 Jun 16. PMID:22765894 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ephrin receptor

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