1ZZ2

Two Classes of p38alpha MAP Kinase Inhibitors Having a Common Diphenylether Core but Exhibiting Divergent Binding Modes

Summary for 1ZZ2

• Entry DOI: 10.2210/pdb1zz2/pdb
• Related: 1ZYJ
• Descriptor: Mitogen-activated protein kinase 14, octyl beta-D-glucopyranoside, N-[3-(4-FLUOROPHENOXY)PHENYL]-4-[(2-HYDROXYBENZYL)AMINO]PIPERIDINE-1-SULFONAMIDE, ... (4 entities in total)
• Functional Keywords: protein-inhibitor complex, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm (By similarity): Q16539
• Total number of polymer chains: 1
• Total formula weight: 42107.11

Authors

Michelotti, E.L.,Moffett, K.K.,Springman, E.B.,Karpusas, M. (deposition date: 2005-06-13, release date: 2005-10-18, Last modification date: 2024-02-14)

Primary citation

Michelotti, E.L.,Moffett, K.K.,Nguyen, D.,Kelly, M.J.,Shetty, R.,Chai, X.,Northrop, K.,Namboodiri, V.,Campbell, B.,Flynn, G.A.,Fujimoto, T.,Hollinger, F.P.,Bukhtiyarova, M.,Springman, E.B.,Karpusas, M.
Two classes of p38alpha MAP kinase inhibitors having a common diphenylether core but exhibiting divergent binding modes.
Bioorg.Med.Chem.Lett., 15:5274-5279, 2005

PubMed Abstract: Two new classes of diphenylether inhibitors of p38alpha MAP kinase are described. Both chemical classes are based on a common diphenylether core that is identified by simulated fragment annealing as one of the most favored chemotypes within a prominent hydrophobic pocket of the p38alpha ATP-binding site. In the fully elaborated molecules, the diphenylether moiety acts as an anchor occupying the deep pocket, while polar extensions make specific interactions with either the adenine binding site or the phosphate binding site of ATP. The synthesis, crystallographic analysis, and biological activity of these p38alpha inhibitors are discussed.

PubMed: 16169718
DOI: 10.1016/j.bmcl.2005.08.038

Experimental method

X-RAY DIFFRACTION (2 Å)