2oh4
From Proteopedia
(New page: 200px<br /> <applet load="2oh4" size="450" color="white" frame="true" align="right" spinBox="true" caption="2oh4, resolution 2.050Å" /> '''Crystal structure ...) |
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| - | [[Image:2oh4. | + | [[Image:2oh4.jpg|left|200px]]<br /><applet load="2oh4" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2oh4" size=" | + | |
caption="2oh4, resolution 2.050Å" /> | caption="2oh4, resolution 2.050Å" /> | ||
'''Crystal structure of Vegfr2 with a benzimidazole-urea inhibitor'''<br /> | '''Crystal structure of Vegfr2 with a benzimidazole-urea inhibitor'''<br /> | ||
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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. | ||
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| - | ==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== | ||
| - | 2OH4 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with SO4 and GIG as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http:// | + | 2OH4 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=GIG:'>GIG</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OH4 OCA]. |
==Reference== | ==Reference== | ||
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[[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:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 13:34:35 2008'' |
Revision as of 11:34, 23 January 2008
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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 with and as ligands. Active as Receptor protein-tyrosine kinase, with EC number 2.7.10.1 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 Wed Jan 23 13:34:35 2008
Categories: Homo sapiens | Receptor protein-tyrosine kinase | Single protein | Nolte, R.T. | Wang, L. | GIG | SO4 | 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
