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PDBsum entry 2h96

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Transcription PDB id
2h96
Jmol
Contents
Protein chains
359 a.a. *
Ligands
PRO-LYS-ARG-PRO-
THR-THR-LEU-ASN-
LEU-PHE
×2
SO4 ×4
893 ×2
GOL ×2
* Residue conservation analysis
PDB id:
2h96
Name: Transcription
Title: Discovery of potent, highly selective, and orally bioavailab pyridine carboxamidE C-jun nh2-terminal kinase inhibitors
Structure: Mitogen-activated protein kinase 8. Chain: a, b. Fragment: jnk1-(1-364)-6his. Synonym: stress-activated protein kinase jnk1, c-jun n-term kinase 1, jnk-46. Engineered: yes. Mutation: yes. C-jun-amino-terminal kinase-interacting protein 1 chain: f, g.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: mapk8, jnk1, prkm8. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: the sequence is found naturally in homo sapi (human).
Biol. unit: Dimer (from PQS)
Resolution:
3.00Å     R-factor:   0.243     R-free:   0.278
Authors: C.Abad-Zapatero
Key ref: H.Zhao et al. (2006). Discovery of potent, highly selective, and orally bioavailable pyridine carboxamide c-Jun NH2-terminal kinase inhibitors. J Med Chem, 49, 4455-4458. PubMed id: 16854050 DOI: 10.1021/jm060465l
Date:
09-Jun-06     Release date:   25-Jul-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P45983  (MK08_HUMAN) -  Mitogen-activated protein kinase 8
Seq:
Struc:
427 a.a.
359 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.2.7.11.24  - Mitogen-activated protein kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a protein = ADP + a phosphoprotein
ATP
+ protein
= ADP
+ phosphoprotein
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     protein phosphorylation   1 term 
  Biochemical function     transferase activity, transferring phosphorus-containing groups     5 terms  

 

 
    reference    
 
 
DOI no: 10.1021/jm060465l J Med Chem 49:4455-4458 (2006)
PubMed id: 16854050  
 
 
Discovery of potent, highly selective, and orally bioavailable pyridine carboxamide c-Jun NH2-terminal kinase inhibitors.
H.Zhao, M.D.Serby, Z.Xin, B.G.Szczepankiewicz, M.Liu, C.Kosogof, B.Liu, L.T.Nelson, E.F.Johnson, S.Wang, T.Pederson, R.J.Gum, J.E.Clampit, D.L.Haasch, C.Abad-Zapatero, E.H.Fry, C.Rondinone, J.M.Trevillyan, H.L.Sham, G.Liu.
 
  ABSTRACT  
 
C-Jun NH2 terminal kinases (JNKs) are important cell signaling enzymes. JNK1 plays a central role in linking obesity and insulin resistance. JNK2 and JNK3 may be involved in inflammatory and neurological disorders, respectively. Small-molecule JNK inhibitors could be valuable tools to study the therapeutic benefits of inhibiting these enzymes and as leads for potential drugs targeting JNKs. In this report, we disclose a series of potent and highly selective JNK inhibitors with good pharmacokinetic profiles.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21276204 J.Du, L.Xi, B.Lei, H.Liu, and X.Yao (2011).
Structural Requirements of Isoquinolones as Novel Selective c-Jun N-terminal Kinase 1 Inhibitors: 2D and 3D QSAR Analyses.
  Chem Biol Drug Des, 77, 248-254.  
21406343 R.M.Mohareb, and H.E.Moustafa (2011).
Use of 2-aminoprop-1-ene-1,1,3-tricarbonitrile for the synthesis of tetrahydronaphthalene, hexahydroisoquinoline and hexahydrocinnoline derivatives with potential antitumor activities.
  Acta Pharm, 61, 51-62.  
21458276 S.K.De, E.Barile, V.Chen, J.L.Stebbins, J.F.Cellitti, T.Machleidt, C.B.Carlson, L.Yang, R.Dahl, and M.Pellecchia (2011).
Design, synthesis, and structure-activity relationship studies of thiophene-3-carboxamide derivatives as dual inhibitors of the c-Jun N-terminal kinase.
  Bioorg Med Chem, 19, 2582-2588.  
20045647 S.K.De, V.Chen, J.L.Stebbins, L.H.Chen, J.F.Cellitti, T.Machleidt, E.Barile, M.Riel-Mehan, R.Dahl, L.Yang, A.Emdadi, R.Murphy, and M.Pellecchia (2010).
Synthesis and optimization of thiadiazole derivatives as a novel class of substrate competitive c-Jun N-terminal kinase inhibitors.
  Bioorg Med Chem, 18, 590-596.  
19947601 T.Kamenecka, R.Jiang, X.Song, D.Duckett, W.Chen, Y.Y.Ling, J.Habel, J.D.Laughlin, J.Chambers, M.Figuera-Losada, M.D.Cameron, L.Lin, C.H.Ruiz, and P.V.LoGrasso (2010).
Synthesis, biological evaluation, X-ray structure, and pharmacokinetics of aminopyrimidine c-jun-N-terminal kinase (JNK) inhibitors.
  J Med Chem, 53, 419-431.
PDB code: 3kvx
19271755 S.K.De, J.L.Stebbins, L.H.Chen, M.Riel-Mehan, T.Machleidt, R.Dahl, H.Yuan, A.Emdadi, E.Barile, V.Chen, R.Murphy, and M.Pellecchia (2009).
Design, synthesis, and structure-activity relationship of substrate competitive, selective, and in vivo active triazole and thiadiazole inhibitors of the c-Jun N-terminal kinase.
  J Med Chem, 52, 1943-1952.  
19282190 S.K.De, L.H.Chen, J.L.Stebbins, T.Machleidt, M.Riel-Mehan, R.Dahl, V.Chen, H.Yuan, E.Barile, A.Emdadi, R.Murphy, and M.Pellecchia (2009).
Discovery of 2-(5-nitrothiazol-2-ylthio)benzo[d]thiazoles as novel c-Jun N-terminal kinase inhibitors.
  Bioorg Med Chem, 17, 2712-2717.  
19261605 T.Kamenecka, J.Habel, D.Duckett, W.Chen, Y.Y.Ling, B.Frackowiak, R.Jiang, Y.Shin, X.Song, and P.Lograsso (2009).
Structure-Activity Relationships and X-ray Structures Describing the Selectivity of Aminopyrazole Inhibitors for c-Jun N-terminal Kinase 3 (JNK3) over p38.
  J Biol Chem, 284, 12853-12861.
PDB codes: 3fi2 3fi3
17907963 B.Salh (2007).
c-Jun N-terminal kinases as potential therapeutic targets.
  Expert Opin Ther Targets, 11, 1339-1353.  
17084612 D.A.Erlanson (2006).
Fragment-based lead discovery: a chemical update.
  Curr Opin Biotechnol, 17, 643-652.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.