2osc
From Proteopedia
(New page: 200px<br /> <applet load="2osc" size="450" color="white" frame="true" align="right" spinBox="true" caption="2osc, resolution 2.8Å" /> '''Synthesis, Structura...) |
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caption="2osc, resolution 2.8Å" /> | caption="2osc, resolution 2.8Å" /> | ||
'''Synthesis, Structural Analysis, and SAR Studies of Triazine Derivatives as Potent, Selective Tie-2 Inhibitors'''<br /> | '''Synthesis, Structural Analysis, and SAR Studies of Triazine Derivatives as Potent, Selective Tie-2 Inhibitors'''<br /> | ||
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==Overview== | ==Overview== | ||
A novel class of selective Tie-2 inhibitors was derived from a, multi-kinase inhibitor 1. By reversing the amide connectivity and, incorporating aminotriazine or aminopyridine hinge-binding moieties, excellent Tie-2 potency and KDR selectivity could be achieved with, 3-substituted terminal aryl rings. X-ray co-crystal structure analysis, aided inhibitor design. This series was evaluated on the basis of potency, selectivity, and rat pharmacokinetic parameters. | A novel class of selective Tie-2 inhibitors was derived from a, multi-kinase inhibitor 1. By reversing the amide connectivity and, incorporating aminotriazine or aminopyridine hinge-binding moieties, excellent Tie-2 potency and KDR selectivity could be achieved with, 3-substituted terminal aryl rings. X-ray co-crystal structure analysis, aided inhibitor design. This series was evaluated on the basis of potency, selectivity, and rat pharmacokinetic parameters. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Venous malformations, multiple cutaneous and mucosal OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600221 600221]] | ||
==About this Structure== | ==About this Structure== | ||
| - | 2OSC 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 MUH as [http://en.wikipedia.org/wiki/ligand ligand]. 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:// | + | 2OSC 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=MUH:'>MUH</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. 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=2OSC OCA]. |
==Reference== | ==Reference== | ||
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[[Category: kinase domain tie-2]] | [[Category: kinase domain tie-2]] | ||
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Revision as of 13:04, 23 January 2008
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Synthesis, Structural Analysis, and SAR Studies of Triazine Derivatives as Potent, Selective Tie-2 Inhibitors
Overview
A novel class of selective Tie-2 inhibitors was derived from a, multi-kinase inhibitor 1. By reversing the amide connectivity and, incorporating aminotriazine or aminopyridine hinge-binding moieties, excellent Tie-2 potency and KDR selectivity could be achieved with, 3-substituted terminal aryl rings. X-ray co-crystal structure analysis, aided inhibitor design. This series was evaluated on the basis of potency, selectivity, and rat pharmacokinetic parameters.
About this Structure
2OSC is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Receptor protein-tyrosine kinase, with EC number 2.7.10.1 Full crystallographic information is available from OCA.
Reference
Synthesis, structural analysis, and SAR studies of triazine derivatives as potent, selective Tie-2 inhibitors., Hodous BL, Geuns-Meyer SD, Hughes PE, Albrecht BK, Bellon S, Caenepeel S, Cee VJ, Chaffee SC, Emery M, Fretland J, Gallant P, Gu Y, Johnson RE, Kim JL, Long AM, Morrison M, Olivieri PR, Patel VF, Polverino A, Rose P, Wang L, Zhao H, Bioorg Med Chem Lett. 2007 May 15;17(10):2886-9. Epub 2007 Feb 25. PMID:17350837
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