2oh4
From Proteopedia
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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. | ||
| - | |||
| - | ==Disease== | ||
| - | Known disease associated with this structure: Hemangioma, capillary infantile, somatic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191306 191306]] | ||
==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: GIG]] | ||
| - | [[Category: SO4]] | ||
[[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'' |
Revision as of 01:17, 31 March 2008
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| , resolution 2.050Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , | ||||||
| Gene: | KDR, FLK1 (Homo sapiens) | ||||||
| Activity: | Receptor protein-tyrosine kinase, with EC number 2.7.10.1 | ||||||
| Related: | 1vr2, 1y6a, 1y6b, 1ywm
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of Vegfr2 with a benzimidazole-urea inhibitor
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.
About this Structure
2OH4 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Discovery of novel benzimidazoles as potent inhibitors of TIE-2 and VEGFR-2 tyrosine kinase receptors., Hasegawa M, Nishigaki N, Washio Y, Kano K, Harris PA, Sato H, Mori I, West RI, Shibahara M, Toyoda H, Wang L, Nolte RT, Veal JM, Cheung M, J Med Chem. 2007 Sep 6;50(18):4453-70. Epub 2007 Aug 4. PMID:17676829
Page seeded by OCA on Mon Mar 31 04:17:50 2008
Categories: Homo sapiens | Receptor protein-tyrosine kinase | Single protein | Nolte, R T. | Wang, L. | Transferase | 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
