2P55
X-ray structure of the human mitogen-activated protein kinase kinase 1 (MEK1) in a complex with ligand and MgATP
Summary for 2P55
| Entry DOI | 10.2210/pdb2p55/pdb |
| Related | 1S9I 1S9J |
| Descriptor | Dual specificity mitogen-activated protein kinase kinase 1, MAGNESIUM ION, 2-[(4-ETHYNYL-2-FLUOROPHENYL)AMINO]-3,4-DIFLUORO-N-(2-HYDROXYETHOXY)BENZAMIDE, ... (5 entities in total) |
| Functional Keywords | protein kinase structure; mitogen activated protein kinase kinase; signal transduction; ligand co-complex, ternary co-complex with kinase, ligand and mgatp; non-competitive protein kinase inhibitor, transferase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 37741.25 |
| Authors | Ohren, J.F.,Pavlovsky, A.G. (deposition date: 2007-03-14, release date: 2007-10-02, Last modification date: 2023-08-30) |
| Primary citation | Spicer, J.A.,Rewcastle, G.W.,Kaufman, M.D.,Black, S.L.,Plummer, M.S.,Denny, W.A.,Quin, J.,Shahripour, A.B.,Barrett, S.D.,Whitehead, C.E.,Milbank, J.B.,Ohren, J.F.,Gowan, R.C.,Omer, C.,Camp, H.S.,Esmaeil, N.,Moore, K.,Sebolt-Leopold, J.S.,Pryzbranowski, S.,Merriman, R.L.,Ortwine, D.F.,Warmus, J.S.,Flamme, C.M.,Pavlovsky, A.G.,Tecle, H. 4-anilino-5-carboxamido-2-pyridone derivatives as noncompetitive inhibitors of mitogen-activated protein kinase kinase. J.Med.Chem., 50:5090-5102, 2007 Cited by PubMed Abstract: A new series of MEK1 inhibitors, the 4-anilino-5-carboxamido-2-pyridones, were designed and synthesized using a combination of medicinal chemistry, computational chemistry, and structural elucidation. The effect of variation in the carboxamide side chain, substitution on the pyridone nitrogen, and replacement of the 4'-iodide were all investigated. This study afforded several compounds which were either equipotent or more potent than the clinical candidate CI-1040 (1) in an isolated enzyme assay, as well as murine colon carcinoma (C26) cells, as measured by suppression of phosphorylated ERK substrate. Most notably, pyridone 27 was found to be more potent than 1 in vitro and produced a 100% response rate at a lower dose than 1, when tested for in vivo efficacy in animals bearing C26 tumors. PubMed: 17880056DOI: 10.1021/jm0704548 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.8 Å) |
Structure validation
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