8OW3
Crystal structure of wild-type c-MET bound by compound 2
Summary for 8OW3
| Entry DOI | 10.2210/pdb8ow3/pdb |
| Descriptor | Hepatocyte growth factor receptor, 5-[3,5-bis(fluoranyl)phenyl]-1-[(1S)-1-phenylethyl]pyrimidine-2,4-dione (3 entities in total) |
| Functional Keywords | kinase, inhibitor, cancer research, drug discovery, transferase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 35170.63 |
| Authors | Collie, G.W. (deposition date: 2023-04-26, release date: 2023-07-05, Last modification date: 2024-06-19) |
| Primary citation | Michaelides, I.N.,Collie, G.W.,Borjesson, U.,Vasalou, C.,Alkhatib, O.,Barlind, L.,Cheung, T.,Dale, I.L.,Embrey, K.J.,Hennessy, E.J.,Khurana, P.,Koh, C.M.,Lamb, M.L.,Liu, J.,Moss, T.A.,O'Neill, D.J.,Phillips, C.,Shaw, J.,Snijder, A.,Storer, R.I.,Stubbs, C.J.,Han, F.,Li, C.,Qiao, J.,Sun, D.Q.,Wang, J.,Wang, P.,Yang, W. Discovery and Optimization of the First ATP Competitive Type-III c-MET Inhibitor. J.Med.Chem., 66:8782-8807, 2023 Cited by PubMed Abstract: Recent clinical reports have highlighted the need for wild-type (WT) and mutant dual inhibitors of c-MET kinase for the treatment of cancer. We report herein a novel chemical series of ATP competitive type-III inhibitors of WT and D1228V mutant c-MET. Using a combination of structure-based drug design and computational analyses, ligand was optimized to a highly selective chemical series with nanomolar activities in biochemical and cellular settings. Representatives of the series demonstrate excellent pharmacokinetic profiles in rat studies with promising free-brain exposures, paving the way for the design of brain permeable drugs for the treatment of c-MET driven cancers. PubMed: 37343272DOI: 10.1021/acs.jmedchem.3c00401 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.27 Å) |
Structure validation
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