1YWR

Crystal Structure Analysis of inactive P38 kinase domain in complex with a Monocyclic Pyrazolone Inhibitor

Summary for 1YWR

• Entry DOI: 10.2210/pdb1ywr/pdb
• Related: 1yw2
• Descriptor: Mitogen-activated protein kinase 14, 4-(4-FLUOROPHENYL)-1-METHYL-5-(2-{[(1S)-1-PHENYLETHYL]AMINO}PYRIMIDIN-4-YL)-2-PIPERIDIN-4-YL-1,2-DIHYDRO-3H-PYRAZOL-3-ONE (3 entities in total)
• Functional Keywords: p38 kinase, moncyclic pyrazolone, transferase
• Biological source: Mus musculus (house mouse)
• Cellular location: Cytoplasm : P47811
• Total number of polymer chains: 1
• Total formula weight: 41794.72

Authors

Golebiowski, A.,Townes, J.A.,Laufersweiler, M.J.,Brugel, T.A.,Clark, M.P.,Clark, C.M.,Djung, J.F.,Laughlin, S.K.,Sabat, M.P.,Bookland, R.G.,Vanrens, J.C.,De, B.,Hsieh, L.C.,Janusz, M.J.,Walter, R.L.,Webster, M.E.,Mekel, M.J. (deposition date: 2005-02-18, release date: 2005-05-10, Last modification date: 2024-02-14)

Primary citation

Golebiowski, A.,Townes, J.A.,Laufersweiler, M.J.,Brugel, T.A.,Clark, M.P.,Clark, C.M.,Djung, J.F.,Laughlin, S.K.,Sabat, M.P.,Bookland, R.G.,Vanrens, J.C.,De, B.,Hsieh, L.C.,Janusz, M.J.,Walter, R.L.,Webster, M.E.,Mekel, M.J.
The development of monocyclic pyrazolone based cytokine synthesis inhibitors.
Bioorg.Med.Chem.Lett., 15:2285-2289, 2005

PubMed Abstract: 4-Aryl-5-pyrimidyl based cytokine synthesis inhibitors that contain a novel monocyclic, pyrazolone heterocyclic core are described. Many of these inhibitors showed low nanomolar activity against LPS-induced TNF-alpha production. One of the compounds (6e) was found to be efficacious in the rat iodoacetate (RIA) in vivo model of osteoarthritis. The X-ray crystal structure of a pyrazolone inhibitor cocrystallized with mutated p38 (mp38) is presented.

PubMed: 15837310
DOI: 10.1016/j.bmcl.2005.03.007

Experimental method

X-RAY DIFFRACTION (1.95 Å)