3GI3

Crystal structure of a N-Phenyl-N'-Naphthylurea analog in complex with p38 MAP kinase

Summary for 3GI3

• Entry DOI: 10.2210/pdb3gi3/pdb
• Descriptor: Mitogen-activated protein kinase 14, N-{5-tert-butyl-2-methoxy-3-[({4-[6-(morpholin-4-ylmethyl)pyridin-3-yl]naphthalen-1-yl}carbamoyl)amino]phenyl}methanesulfonamide (3 entities in total)
• Functional Keywords: two lobe kinase structure, n-lobe beta-sheet, c-lobe alpha-helix, alternative splicing, atp-binding, cytoplasm, kinase, nucleotide-binding, nucleus, phosphoprotein, polymorphism, serine/threonine-protein kinase, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm (By similarity): Q16539
• Total number of polymer chains: 1
• Total formula weight: 42092.07

Authors

Qian, K.C. (deposition date: 2009-03-05, release date: 2009-10-20, Last modification date: 2024-02-21)

Primary citation

Cirillo, P.F.,Hickey, E.R.,Moss, N.,Breitfelder, S.,Betageri, R.,Fadra, T.,Gaenzler, F.,Gilmore, T.,Goldberg, D.R.,Kamhi, V.,Kirrane, T.,Kroe, R.R.,Madwed, J.,Moriak, M.,Netherton, M.,Pargellis, C.A.,Patel, U.R.,Qian, K.C.,Sharma, R.,Sun, S.,Swinamer, A.,Torcellini, C.,Takahashi, H.,Tsang, M.,Xiong, Z.
Discovery and characterization of the N-phenyl-N'-naphthylurea class of p38 kinase inhibitors.
Bioorg.Med.Chem.Lett., 19:2386-2391, 2009

PubMed Abstract: An effort aimed at exploring structural diversity in the N-pyrazole-N'-naphthylurea class of p38 kinase inhibitors led to the synthesis and characterization of N-phenyl-N'-naphthylureas. Examples of these compounds displayed excellent inhibition of TNF-alpha production in vitro, as well as efficacy in a mouse model of lipopolysaccharide induced endotoxemia. In addition, perspective is provided on the role of a sulfonamide functionality in defining inhibitor potency.

PubMed: 19356929
DOI: 10.1016/j.bmcl.2009.03.104

Experimental method

X-RAY DIFFRACTION (2.4 Å)