3UVP
Human p38 MAP Kinase in Complex with a Benzamide Substituted Benzosuberone
Summary for 3UVP
| Entry DOI | 10.2210/pdb3uvp/pdb |
| Related | 3QUD 3QUE 3UVQ 3UVR 3UVS |
| Descriptor | Mitogen-activated protein kinase 14, N-{2-fluoro-5-[(5-oxo-6,7,8,9-tetrahydro-5H-benzo[7]annulen-2-yl)amino]phenyl}benzamide, octyl beta-D-glucopyranoside, ... (4 entities in total) |
| Functional Keywords | protein kinase, selective p38 inhibitor, sar, benzosuberon derivative, transferase-transferase inhibitor complex, transferase/transferase inhibitor |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 42242.23 |
| Authors | Mayer-Wrangowski, S.C.,Richters, A.,Gruetter, C.,Rauh, D. (deposition date: 2011-11-30, release date: 2012-11-07, Last modification date: 2023-11-08) |
| Primary citation | Martz, K.E.,Dorn, A.,Baur, B.,Schattel, V.,Goettert, M.I.,Mayer-Wrangowski, S.C.,Rauh, D.,Laufer, S.A. Targeting the Hinge Glycine Flip and the Activation Loop: Novel Approach to Potent p38 alpha Inhibitors. J.Med.Chem., 55:7862-7874, 2012 Cited by PubMed Abstract: The p38 MAP kinase is a key player in signaling pathways regulating the biosynthesis of inflammatory cytokines. Small molecule p38 inhibitors suppress the production of these cytokines. Therefore p38 is a promising drug target for novel anti-inflammatory drugs. In this study, we report novel dibenzepinones, dibenzoxepines, and benzosuberones as p38α MAP kinase inhibitors. Previously reported dibenzepinones and dibenzoxepines were chemically modified by introduction of functional groups or removal of a phenyl ring. This should result in targeting of the hydrophobic region I, the "deep pocket", and the hinge glycine flip of the kinase. Potent inhibitors with IC(50) values in the single digit nanomolar range (up to 3 nM) were identified. Instead of targeting the "deep pocket" in the DFG-out conformation, interactions with the DFG-motif in the in-conformation could be observed by protein X-ray crystallography. PubMed: 22897496DOI: 10.1021/jm300951u PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.4 Å) |
Structure validation
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