2oh4: Difference between revisions
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|PDB= 2oh4 |SIZE=350|CAPTION= <scene name='initialview01'>2oh4</scene>, resolution 2.050Å | |PDB= 2oh4 |SIZE=350|CAPTION= <scene name='initialview01'>2oh4</scene>, resolution 2.050Å | ||
|SITE= | |SITE= | ||
|LIGAND= | |LIGAND= <scene name='pdbligand=GIG:METHYL+(5-{4-[({[2-FLUORO-5-(TRIFLUOROMETHYL)PHENYL]AMINO}CARBONYL)AMINO]PHENOXY}-1H-BENZIMIDAZOL-2-YL)CARBAMATE'>GIG</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> | ||
|ACTIVITY= [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] | |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> | ||
|GENE= KDR, FLK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= KDR, FLK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
|DOMAIN= | |||
|RELATEDENTRY=[[1vr2|1vr2]], [[1y6a|1y6a]], [[1y6b|1y6b]], [[1ywm|1ywm]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2oh4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2oh4 OCA], [http://www.ebi.ac.uk/pdbsum/2oh4 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2oh4 RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==Overview== | ||
We herein disclose a novel chemical series of benzimidazole-ureas as inhibitors of VEGFR-2 and TIE-2 kinase receptors, both of which are implicated in angiogenesis. Structure-activity relationship (SAR) studies elucidated a critical role for the N1 nitrogen of both the benzimidazole (segment E) and urea (segment B) moieties. The SAR results were also supported by the X-ray crystallographic elucidation of the role of the N1 nitrogen and the urea moiety when the benzimidazole-urea compounds were bound to the VEGFR-2 enzyme. The left side phenyl ring (segment A) occupies the backpocket where a 3-hydrophobic substituent was favored for TIE-2 activity. | We herein disclose a novel chemical series of benzimidazole-ureas as inhibitors of VEGFR-2 and TIE-2 kinase receptors, both of which are implicated in angiogenesis. Structure-activity relationship (SAR) studies elucidated a critical role for the N1 nitrogen of both the benzimidazole (segment E) and urea (segment B) moieties. The SAR results were also supported by the X-ray crystallographic elucidation of the role of the N1 nitrogen and the urea moiety when the benzimidazole-urea compounds were bound to the VEGFR-2 enzyme. The left side phenyl ring (segment A) occupies the backpocket where a 3-hydrophobic substituent was favored for TIE-2 activity. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Nolte, R T.]] | [[Category: Nolte, R T.]] | ||
[[Category: Wang, L.]] | [[Category: Wang, L.]] | ||
[[Category: transferase]] | [[Category: transferase]] | ||
[[Category: vascular endothelial growth factor receptor 2 tyrosine-protein kinase 3d-structure vegfr2 angiogenesis atp-binding phosphorylation ec 2 7.1 112 vegfr-2 kinase insert domain receptor protein-tyrosine kinase receptor flk-1]] | [[Category: vascular endothelial growth factor receptor 2 tyrosine-protein kinase 3d-structure vegfr2 angiogenesis atp-binding phosphorylation ec 2 7.1 112 vegfr-2 kinase insert domain receptor protein-tyrosine kinase receptor flk-1]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:17:50 2008'' | ||
