2GHL

Mutant Mus Musculus P38 Kinase Domain in Complex with Inhibitor PG-874743

Summary for 2GHL

• Entry DOI: 10.2210/pdb2ghl/pdb
• Related: 1YW2 1YWR
• Descriptor: Mitogen-activated protein kinase 14, 3-(2-CHLOROPHENYL)-1-(2-{[(1S)-2-HYDROXY-1,2-DIMETHYLPROPYL]AMINO}PYRIMIDIN-4-YL)-1-(4-METHOXYPHENYL)UREA (3 entities in total)
• Functional Keywords: map kinase p38, p38, transferase
• Biological source: Mus musculus (house mouse)
• Cellular location: Cytoplasm : P47811
• Total number of polymer chains: 1
• Total formula weight: 40310.57

Authors

Walter, R.L.,Mekel, M.J.,Evdokimov, A.G.,Pokross, M.E.,Brugel, T.A. (deposition date: 2006-03-27, release date: 2006-04-11, Last modification date: 2024-02-14)

Primary citation

Brugel, T.A.,Maier, J.A.,Clark, M.P.,Sabat, M.,Golebiowski, A.,Bookland, R.G.,Laufersweiler, M.J.,Laughlin, S.K.,Vanrens, J.C.,De, B.,Hsieh, L.C.,Mekel, M.J.,Janusz, M.J.
Development of N-2,4-pyrimidine-N-phenyl-N'-phenyl ureas as inhibitors of tumor necrosis factor alpha (TNF-alpha) synthesis. Part 1.
Bioorg.Med.Chem.Lett., 16:3510-3513, 2006

PubMed Abstract: A new class of tumor necrosis factor alpha (TNF-alpha) synthesis inhibitors based on an N-2,4-pyrimidine-N-phenyl-N'-phenyl urea scaffold is described. Many of these compounds showed low-nanomolar activity against lipopolysaccharide stimulated TNF-alpha production. X-ray co-crystallization studies with mutated p38alpha showed that these trisubstituted ureas interact with the ATP-binding pocket in a pseudo-bicyclic conformation brought about by the presence of an intramolecular hydrogen bonding interaction.

PubMed: 16632356
DOI: 10.1016/j.bmcl.2006.03.095

Experimental method

X-RAY DIFFRACTION (2.099 Å)