2osc
From Proteopedia
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|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=MUH:N-{4-METHYL-3-[(3-PYRIMIDIN-4-YLPYRIDIN-2-YL)AMINO]PHENYL}-3-(TRIFLUOROMETHYL)BENZAMIDE'>MUH</scene> | |LIGAND= <scene name='pdbligand=MUH:N-{4-METHYL-3-[(3-PYRIMIDIN-4-YLPYRIDIN-2-YL)AMINO]PHENYL}-3-(TRIFLUOROMETHYL)BENZAMIDE'>MUH</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= TEK, TIE2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= TEK, TIE2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[2oo8|2OO8]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2osc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2osc OCA], [http://www.ebi.ac.uk/pdbsum/2osc PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2osc RCSB]</span> | ||
}} | }} | ||
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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== | ||
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[[Category: Bellon, S F.]] | [[Category: Bellon, S F.]] | ||
[[Category: Kim, J.]] | [[Category: Kim, J.]] | ||
| - | [[Category: MUH]] | ||
[[Category: kinase domain tie-2]] | [[Category: kinase domain tie-2]] | ||
| - | ''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 04:22:25 2008'' |
Revision as of 01:22, 31 March 2008
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| , resolution 2.8Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | TEK, TIE2 (Homo sapiens) | ||||||
| Activity: | Receptor protein-tyrosine kinase, with EC number 2.7.10.1 | ||||||
| Related: | 2OO8
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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. 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
Page seeded by OCA on Mon Mar 31 04:22:25 2008
