3EFK
Structure of c-Met with pyrimidone inhibitor 50
Summary for 3EFK
| Entry DOI | 10.2210/pdb3efk/pdb |
| Related | 3efj |
| Descriptor | Hepatocyte growth factor receptor, 5-{4-[(6,7-dimethoxyquinolin-4-yl)oxy]-3-fluorophenyl}-2-[(4-fluorophenyl)amino]-3-methylpyrimidin-4(3H)-one (3 entities in total) |
| Functional Keywords | c-met, kinase inhibitor pyrimidone, alternative splicing, atp-binding, chromosomal rearrangement, disease mutation, glycoprotein, kinase, membrane, nucleotide-binding, phosphoprotein, polymorphism, proto-oncogene, receptor, transferase, transmembrane, tyrosine-protein kinase |
| Biological source | Homo sapiens (Human) |
| Cellular location | Membrane; Single-pass type I membrane protein: P08581 |
| Total number of polymer chains | 2 |
| Total formula weight | 71726.81 |
| Authors | Bellon, S.F.,D'Angelo, N.,Whittington, D.,Dussault, I. (deposition date: 2008-09-09, release date: 2008-10-07, Last modification date: 2023-08-30) |
| Primary citation | D'Angelo, N.D.,Bellon, S.F.,Booker, S.K.,Cheng, Y.,Coxon, A.,Dominguez, C.,Fellows, I.,Hoffman, D.,Hungate, R.,Kaplan-Lefko, P.,Lee, M.R.,Li, C.,Liu, L.,Rainbeau, E.,Reider, P.J.,Rex, K.,Siegmund, A.,Sun, Y.,Tasker, A.S.,Xi, N.,Xu, S.,Yang, Y.,Zhang, Y.,Burgess, T.L.,Dussault, I.,Kim, T.S. Design, synthesis, and biological evaluation of potent c-Met inhibitors. J.Med.Chem., 51:5766-5779, 2008 Cited by PubMed Abstract: c-Met is a receptor tyrosine kinase that plays a key role in several cellular processes but has also been found to be overexpressed and mutated in different human cancers. Consequently, targeting this enzyme has become an area of intense research in drug discovery. Our studies began with the design and synthesis of novel pyrimidone 7, which was found to be a potent c-Met inhibitor. Subsequent SAR studies identified 22 as a more potent analog, whereas an X-ray crystal structure of 7 bound to c-Met revealed an unexpected binding conformation. This latter finding led to the development of a new series that featured compounds that were more potent both in vitro and in vivo than 22 and also exhibited different binding conformations to c-Met. Novel c-Met inhibitors have been designed, developed, and found to be potent in vitro and in vivo. PubMed: 18763753DOI: 10.1021/jm8006189 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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