3UVQ
Human p38 MAP Kinase in Complex with a Dibenzosuberone Derivative
Summary for 3UVQ
| Entry DOI | 10.2210/pdb3uvq/pdb |
| Related | 3QUD 3QUE 3UVP 3UVR 3UVS |
| Descriptor | Mitogen-activated protein kinase 14, N-{5-[(7-{[(2R)-2,3-dihydroxypropyl]oxy}-5-oxo-10,11-dihydro-5H-dibenzo[a,d][7]annulen-2-yl)amino]-2-fluorophenyl}benzamide, octyl beta-D-glucopyranoside, ... (4 entities in total) |
| Functional Keywords | selective p38 inhibitor, sar, dibenzosuberone derivative, protein kinase, transferase-transferase inhibitor complex, transferase/transferase inhibitor |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 42087.98 |
| Authors | Mayer-Wrangowski, S.C.,Richters, A.,Gruetter, C.,Rauh, D. (deposition date: 2011-11-30, release date: 2012-12-05, Last modification date: 2023-11-08) |
| Primary citation | Fischer, S.,Wentsch, H.K.,Mayer-Wrangowski, S.C.,Zimmermann, M.,Bauer, S.M.,Storch, K.,Niess, R.,Koeberle, S.C.,Grutter, C.,Boeckler, F.M.,Rauh, D.,Laufer, S.A. Dibenzosuberones as p38 mitogen-activated protein kinase inhibitors with low ATP competitiveness and outstanding whole blood activity. J.Med.Chem., 56:241-253, 2013 Cited by PubMed Abstract: p38α mitogen-activated protein (MAP) kinase is a main target in drug research concerning inflammatory diseases. Nevertheless, no inhibitor of p38α MAP kinase has been introduced to the market. This might be attributed to the fact that there is no inhibitor which combines outstanding activity in biological systems and selectivity. Herein an approach to the development of such inhibitors on the basis of the highly selective molecular probe Skepinone-L is described. Introduction of a "deep pocket" moiety addressing the DFG motif led to an increased activity of the compounds. Hydrophilic moieties, addressing the solvent-exposed area adjacent to hydrophilic region II, conserved a high activity of the compounds in a whole blood assay. Combined with their outstanding selectivity and low ATP competitiveness, these inhibitors are very interesting candidates for use in biological systems and in therapy. PubMed: 23270382DOI: 10.1021/jm301539x PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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