2gmx: Difference between revisions
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|PDB= 2gmx |SIZE=350|CAPTION= <scene name='initialview01'>2gmx</scene>, resolution 3.50Å | |PDB= 2gmx |SIZE=350|CAPTION= <scene name='initialview01'>2gmx</scene>, resolution 3.50Å | ||
|SITE= | |SITE= | ||
|LIGAND= | |LIGAND= <scene name='pdbligand=877:N-(4-AMINO-5-CYANO-6-ETHOXYPYRIDIN-2-YL)-2-(4-BROMO-2,5-DIMETHOXYPHENYL)ACETAMIDE'>877</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> | ||
|ACTIVITY= [http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase Mitogen-activated protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.24 2.7.11.24] | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase Mitogen-activated protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.24 2.7.11.24] </span> | ||
|GENE= MAPK8, JNK1, PRKM8 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= MAPK8, JNK1, PRKM8 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
|DOMAIN= | |||
|RELATEDENTRY=[[2g01|2g01]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2gmx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gmx OCA], [http://www.ebi.ac.uk/pdbsum/2gmx PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2gmx RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==Overview== | ||
The c-Jun N-terminal kinases (JNK-1, -2, and -3) are members of the mitogen activated protein (MAP) kinase family of enzymes. They are activated in response to certain cytokines, as well as by cellular stresses including chemotoxins, peroxides, and irradiation. They have been implicated in the pathology of a variety of different diseases with an inflammatory component including asthma, stroke, Alzheimer's disease, and type 2 diabetes mellitus. In this work, high-throughput screening identified a JNK inhibitor with an excellent kinase selectivity profile. Using X-ray crystallography and biochemical screening to guide our lead optimization, we prepared compounds with inhibitory potencies in the low-double-digit nanomolar range, activity in whole cells, and pharmacokinetics suitable for in vivo use. The new compounds were over 1,000-fold selective for JNK-1 and -2 over other MAP kinases including ERK2, p38alpha, and p38delta and showed little inhibitory activity against a panel of 74 kinases. | The c-Jun N-terminal kinases (JNK-1, -2, and -3) are members of the mitogen activated protein (MAP) kinase family of enzymes. They are activated in response to certain cytokines, as well as by cellular stresses including chemotoxins, peroxides, and irradiation. They have been implicated in the pathology of a variety of different diseases with an inflammatory component including asthma, stroke, Alzheimer's disease, and type 2 diabetes mellitus. In this work, high-throughput screening identified a JNK inhibitor with an excellent kinase selectivity profile. Using X-ray crystallography and biochemical screening to guide our lead optimization, we prepared compounds with inhibitory potencies in the low-double-digit nanomolar range, activity in whole cells, and pharmacokinetics suitable for in vivo use. The new compounds were over 1,000-fold selective for JNK-1 and -2 over other MAP kinases including ERK2, p38alpha, and p38delta and showed little inhibitory activity against a panel of 74 kinases. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Abad-Zapatero, C.]] | [[Category: Abad-Zapatero, C.]] | ||
[[Category: aminopyridine-based c-jun n-terminal kinase inhibitor]] | [[Category: aminopyridine-based c-jun n-terminal kinase inhibitor]] | ||
[[Category: c-jun n-terminal kinase]] | [[Category: c-jun n-terminal kinase]] | ||
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[[Category: protein kinase jnk1 inhibitor]] | [[Category: protein kinase jnk1 inhibitor]] | ||
''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 03:18:53 2008'' | ||