2I0H

The structure of p38alpha in complex with an arylpyridazinone

Summary for 2I0H

• Entry DOI: 10.2210/pdb2i0h/pdb
• Descriptor: Mitogen-activated protein kinase 14, 2-(3-{(2-CHLORO-4-FLUOROPHENYL)[1-(2-CHLOROPHENYL)-6-OXO-1,6-DIHYDROPYRIDAZIN-3-YL]AMINO}PROPYL)-1H-ISOINDOLE-1,3(2H)-DIONE, GLYCEROL, ... (4 entities in total)
• Functional Keywords: serine/threonine kinase, inhibitor design, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : Q16539
• Total number of polymer chains: 1
• Total formula weight: 43241.80

Authors

Natarajan, S.R.,Heller, S.T.,Nam, K.,Singh, S.B.,Scapin, G.,Patel, S.,Thompson, J.E.,Fitzgerald, C.E.,O'Keefe, S.J. (deposition date: 2006-08-10, release date: 2006-10-17, Last modification date: 2023-08-30)

Primary citation

Natarajan, S.R.,Heller, S.T.,Nam, K.,Singh, S.B.,Scapin, G.,Patel, S.,Fitzgerald, C.E.,Thompson, J.E.,O'Keefe, S.J.
p38 MAP Kinase Inhibitors Part 6: 2-Arylpyridazin-3-ones as templates for inhibitor design.
Bioorg.Med.Chem.Lett., 16:5809-5813, 2006

PubMed Abstract: p38 inhibitors based on 3,4-dihydropyrido[4,3-d]pyrimidazin-2-one template were synthesized and their SAR explored. Benchmark compounds 30, 35, and 36 were found to be potent against the enzyme. Crystal structure of p38 in complex with 30 indicated a key pi-stacking interaction with the pendant tyrosine residue-35 in the glycine-rich loop.

PubMed: 16945533
DOI: 10.1016/j.bmcl.2006.08.074

Experimental method

X-RAY DIFFRACTION (2 Å)