2xvd

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2xvd, resolution 1.70Å ()
Ligands: ,
Activity: Receptor protein-tyrosine kinase, with EC number 2.7.10.1
Related: 2x9f, 2bba, 2vwu, 2vx0, 2vwv, 2vwz, 2vwy, 2vww, 2vwx, 2vx1


Resources: FirstGlance, OCA, RCSB, PDBsum
Coordinates: save as pdb, mmCIF, xml


Contents

EPHB4 KINASE DOMAIN INHIBITOR COMPLEX

Publication Abstract from PubMed

Optimization of our bis-anilino-pyrimidine series of EphB4 kinase inhibitors led to the discovery of compound 12 which incorporates a key m-hydroxymethylene group on the C4 aniline. 12 displays a good kinase selectivity profile, good physical properties and pharmacokinetic parameters, suggesting it is a suitable candidate to investigate the therapeutic potential of EphB4 kinase inhibitors.

Inhibitors of the tyrosine kinase EphB4. Part 4: Discovery and optimization of a benzylic alcohol series., Barlaam B, Ducray R, Lambert-van der Brempt C, Ple P, Bardelle C, Brooks N, Coleman T, Cross D, Kettle JG, Read J, Bioorg Med Chem Lett. 2011 Apr 15;21(8):2207-11. PMID:21441027

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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.[1] [2]

About this Structure

2xvd is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

  • Barlaam B, Ducray R, Lambert-van der Brempt C, Ple P, Bardelle C, Brooks N, Coleman T, Cross D, Kettle JG, Read J. Inhibitors of the tyrosine kinase EphB4. Part 4: Discovery and optimization of a benzylic alcohol series. Bioorg Med Chem Lett. 2011 Apr 15;21(8):2207-11. PMID:21441027 doi:10.1016/j.bmcl.2011.03.009
  1. Fuller T, Korff T, Kilian A, Dandekar G, Augustin HG. Forward EphB4 signaling in endothelial cells controls cellular repulsion and segregation from ephrinB2 positive cells. J Cell Sci. 2003 Jun 15;116(Pt 12):2461-70. Epub 2003 May 6. PMID:12734395 doi:10.1242/jcs.00426
  2. Erber R, Eichelsbacher U, Powajbo V, Korn T, Djonov V, Lin J, Hammes HP, Grobholz R, Ullrich A, Vajkoczy P. EphB4 controls blood vascular morphogenesis during postnatal angiogenesis. EMBO J. 2006 Feb 8;25(3):628-41. Epub 2006 Jan 19. PMID:16424904 doi:10.1038/sj.emboj.7600949

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