2p4i

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[[Image:2p4i.gif|left|200px]]
[[Image:2p4i.gif|left|200px]]
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{{Structure
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<!--
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|PDB= 2p4i |SIZE=350|CAPTION= <scene name='initialview01'>2p4i</scene>, resolution 2.50&Aring;
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The line below this paragraph, containing "STRUCTURE_2p4i", creates the "Structure Box" on the page.
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|SITE=
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=MR9:4-METHYL-3-({3-[2-(METHYLAMINO)PYRIMIDIN-4-YL]PYRIDIN-2-YL}OXY)-N-[2-MORPHOLIN-4-YL-5-(TRIFLUOROMETHYL)PHENYL]BENZAMIDE'>MR9</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span>
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or leave the SCENE parameter empty for the default display.
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|GENE= TEK, TIE2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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-->
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|DOMAIN=
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{{STRUCTURE_2p4i| PDB=2p4i | SCENE= }}
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|RELATEDENTRY=[[2oo8|2OO8]]
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2p4i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p4i OCA], [http://www.ebi.ac.uk/pdbsum/2p4i PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2p4i RCSB]</span>
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}}
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'''Evolution of a highly Selective and Potent 2-(Pyridin-2-yl)-1,3,5-triazine Tie-2 Kinase Inhibitor'''
'''Evolution of a highly Selective and Potent 2-(Pyridin-2-yl)-1,3,5-triazine Tie-2 Kinase Inhibitor'''
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[[Category: Single protein]]
[[Category: Single protein]]
[[Category: Bellon, S F.]]
[[Category: Bellon, S F.]]
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[[Category: tie-2 kinase inhibitor triazine]]
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[[Category: Tie-2 kinase inhibitor triazine]]
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[[Category: transferase]]
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[[Category: Transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 12:20:30 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:29:22 2008''
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Revision as of 09:20, 4 May 2008

Image:2p4i.gif

Template:STRUCTURE 2p4i

Evolution of a highly Selective and Potent 2-(Pyridin-2-yl)-1,3,5-triazine Tie-2 Kinase Inhibitor


Overview

Inhibition of angiogenesis is a promising and clinically validated approach for limiting tumor growth and survival. The receptor tyrosine kinase Tie-2 is expressed almost exclusively in the vascular endothelium and is required for developmental angiogenesis and vessel maturation. However, the significance of Tie-2 signaling in tumor angiogenesis is not well understood. In order to evaluate the therapeutic utility of inhibiting Tie-2 signaling, we developed a series of potent and orally bioavailable small molecule Tie-2 kinase inhibitors with selectivity over other kinases, especially those that are believed to be important for tumor angiogenesis. Our earlier work provided pyridinyl pyrimidine 6 as a potent, nonselective Tie-2 inhibitor that was designed on the basis of X-ray cocrystal structures of KDR inhibitors 34 (triazine) and 35 (nicotinamide). Lead optimization resulted in pyridinyl triazine 63, which exhibited >30-fold selectivity over a panel of kinases, good oral exposure, and in vivo inhibition of Tie-2 phosphorylation.

About this Structure

2P4I is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Evolution of a highly selective and potent 2-(pyridin-2-yl)-1,3,5-triazine Tie-2 kinase inhibitor., Hodous BL, Geuns-Meyer SD, Hughes PE, Albrecht BK, Bellon S, Bready J, Caenepeel S, Cee VJ, Chaffee SC, Coxon A, Emery M, Fretland J, Gallant P, Gu Y, Hoffman D, Johnson RE, Kendall R, Kim JL, Long AM, Morrison M, Olivieri PR, Patel VF, Polverino A, Rose P, Tempest P, Wang L, Whittington DA, Zhao H, J Med Chem. 2007 Feb 22;50(4):611-26. Epub 2007 Jan 25. PMID:17253678 Page seeded by OCA on Sun May 4 12:20:30 2008

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OCA

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