2oh4: Difference between revisions
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New page: left|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. | ||
==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]] | ||
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