3S3I

p38 kinase crystal structure in complex with small molecule inhibitor

Summary for 3S3I

• Entry DOI: 10.2210/pdb3s3i/pdb
• Descriptor: Mitogen-activated protein kinase 14, 3-(3-tert-butyl[1,2,4]triazolo[4,3-a]pyridin-7-yl)-N-cyclopropyl-4-methylbenzamide (3 entities in total)
• Functional Keywords: p38 map kinase, inhibitor, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: Q16539
• Total number of polymer chains: 1
• Total formula weight: 40383.25

Authors

Segarra, V.,Aiguade, J.,Roca, R.,Fisher, M.,Lamers, M. (deposition date: 2011-05-18, release date: 2012-04-04, Last modification date: 2023-09-13)

Primary citation

Aiguade, J.,Balague, C.,Carranco, I.,Caturla, F.,Dominguez, M.,Eastwood, P.,Esteve, C.,Gonzalez, J.,Lumeras, W.,Orellana, A.,Preciado, S.,Roca, R.,Vidal, L.,Vidal, B.
Novel triazolopyridylbenzamides as potent and selective p38 alpha inhibitors.
Bioorg.Med.Chem.Lett., 22:3431-3436, 2012

PubMed Abstract: A new class of p38α inhibitors based on a biaryl-triazolopyridine scaffold was investigated. X-ray crystallographic data of the initial lead compound cocrystallised with p38α was crucial in order to uncover a unique binding mode of the inhibitor to the hinge region via a pair of water molecules. Synthesis and SAR was directed towards the improvement of binding affinity, as well as ADME properties for this new class of p38α inhibitors and ultimately afforded compounds showing good in vivo efficacy.

PubMed: 22521646
DOI: 10.1016/j.bmcl.2012.03.099

Experimental method

X-RAY DIFFRACTION (1.8 Å)