2gmx
From Proteopedia
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| - | [[Image:2gmx.gif|left|200px]] | + | [[Image:2gmx.gif|left|200px]] |
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| - | '''Selective Aminopyridine-Based C-Jun N-terminal Kinase inhibitors with cellular activity''' | + | {{Structure |
| + | |PDB= 2gmx |SIZE=350|CAPTION= <scene name='initialview01'>2gmx</scene>, resolution 3.50Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> and <scene name='pdbligand=877:N-(4-AMINO-5-CYANO-6-ETHOXYPYRIDIN-2-YL)-2-(4-BROMO-2,5-DIMETHOXYPHENYL)ACETAMIDE'>877</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] | ||
| + | |GENE= MAPK8, JNK1, PRKM8 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''Selective Aminopyridine-Based C-Jun N-terminal Kinase inhibitors with cellular activity''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2GMX is a [ | + | 2GMX is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GMX OCA]. |
==Reference== | ==Reference== | ||
| - | Aminopyridine-based c-Jun N-terminal kinase inhibitors with cellular activity and minimal cross-kinase activity., Szczepankiewicz BG, Kosogof C, Nelson LT, Liu G, Liu B, Zhao H, Serby MD, Xin Z, Liu M, Gum RJ, Haasch DL, Wang S, Clampit JE, Johnson EF, Lubben TH, Stashko MA, Olejniczak ET, Sun C, Dorwin SA, Haskins K, Abad-Zapatero C, Fry EH, Hutchins CW, Sham HL, Rondinone CM, Trevillyan JM, J Med Chem. 2006 Jun 15;49(12):3563-80. PMID:[http:// | + | Aminopyridine-based c-Jun N-terminal kinase inhibitors with cellular activity and minimal cross-kinase activity., Szczepankiewicz BG, Kosogof C, Nelson LT, Liu G, Liu B, Zhao H, Serby MD, Xin Z, Liu M, Gum RJ, Haasch DL, Wang S, Clampit JE, Johnson EF, Lubben TH, Stashko MA, Olejniczak ET, Sun C, Dorwin SA, Haskins K, Abad-Zapatero C, Fry EH, Hutchins CW, Sham HL, Rondinone CM, Trevillyan JM, J Med Chem. 2006 Jun 15;49(12):3563-80. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16759099 16759099] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Mitogen-activated protein kinase]] | [[Category: Mitogen-activated protein kinase]] | ||
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[[Category: 877]] | [[Category: 877]] | ||
[[Category: SO4]] | [[Category: SO4]] | ||
| - | [[Category: aminopyridine-based c-jun n-terminal kinase | + | [[Category: aminopyridine-based c-jun n-terminal kinase inhibitor]] |
[[Category: c-jun n-terminal kinase]] | [[Category: c-jun n-terminal kinase]] | ||
[[Category: jnk1]] | [[Category: jnk1]] | ||
| - | [[Category: protein kinase jnk1 | + | [[Category: protein kinase jnk1 inhibitor]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:06:36 2008'' |
Revision as of 15:06, 20 March 2008
| |||||||
| , resolution 3.50Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Gene: | MAPK8, JNK1, PRKM8 (Homo sapiens) | ||||||
| Activity: | Mitogen-activated protein kinase, with EC number 2.7.11.24 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Selective Aminopyridine-Based C-Jun N-terminal Kinase inhibitors with cellular activity
Contents |
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.
Disease
Known diseases associated with this structure: Diabetes mellitus, noninsulin-dependent OMIM:[604641]
About this Structure
2GMX is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Aminopyridine-based c-Jun N-terminal kinase inhibitors with cellular activity and minimal cross-kinase activity., Szczepankiewicz BG, Kosogof C, Nelson LT, Liu G, Liu B, Zhao H, Serby MD, Xin Z, Liu M, Gum RJ, Haasch DL, Wang S, Clampit JE, Johnson EF, Lubben TH, Stashko MA, Olejniczak ET, Sun C, Dorwin SA, Haskins K, Abad-Zapatero C, Fry EH, Hutchins CW, Sham HL, Rondinone CM, Trevillyan JM, J Med Chem. 2006 Jun 15;49(12):3563-80. PMID:16759099
Page seeded by OCA on Thu Mar 20 17:06:36 2008
