4E73: Crystal Structure Of Jnk1beta-jip In Complex With An Azaquinolone Inhbitor

Citation:
Abstract
3-[4-((1S,2S,3R,5S,7S)-5-Hydroxyadamantan-2-ylcarbamoyl)benzyl]-4-oxo-1-phenyl-1,4-dihydro-[1,8]naphthyridine-2-carboxylic acid methyl ester (4) was identified as a novel, druglike and selective quinolone pan JNK inhibitor. In this communication, some of the structure-activity relationship of the azaquinolone analogues leading to 4 is discussed. The focus is on how changes at the amide functionality affected the biochemical potency, cellular potency, metabolic properties, and solubility of this class of JNK inhibitors. Optimization of these properties led to the identification of the adamantyl analogue, 4. 4 achieved proof of mechanism in both rat and mouse TNF-alpha challenge models.
PDB ID: 4E73Download
MMDB ID: 110489
PDB Deposition Date: 2012/3/16
Updated in MMDB: 2014/10
Experimental Method:
x-ray diffraction
Resolution: 2.27  Å
Source Organism:
Similar Structures:
Biological Unit for 4E73: dimeric; determined by author and by software (PISA)
Molecular Components in 4E73
Label Count Molecule
Proteins (2 molecules)
1
Mitogen-activated Protein Kinase 8(Gene symbol: MAPK8)
Molecule annotation
1
C-jun-amino-terminal Kinase-interacting Protein 1(Gene symbol: MAPK8IP1)
Molecule annotation
Chemical (1 molecule)
1
1
* Click molecule labels to explore molecular sequence information.

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