7OXB
Crystal structure of EGFR double mutant (T790M/L858R) in complex with compound 6.
Summary for 7OXB
| Entry DOI | 10.2210/pdb7oxb/pdb |
| Descriptor | Epidermal growth factor receptor, 2-[2-(3-methoxyphenyl)pyrimidin-4-yl]-1'-prop-2-enoyl-spiro[5,6-dihydro-1~{H}-pyrrolo[3,2-c]pyridine-7,4'-piperidine]-4-one (3 entities in total) |
| Functional Keywords | kinase, inhibitor, egfr, mutant, transferase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 37767.77 |
| Authors | Collie, G.W. (deposition date: 2021-06-22, release date: 2021-10-20, Last modification date: 2024-11-13) |
| Primary citation | Hoogenboom, N.,Demont, D.,de Zwart, E.,Verkaik, S.,Emmelot, M.,van de Kar, B.,Kaptein, A.,Barf, T. Discovery and optimization of covalent EGFR T790M/L858R mutant inhibitors". Bioorg.Med.Chem.Lett., :128406-128406, 2021 Cited by PubMed Abstract: Epidermal growth factor receptor (EGFR) inhibitors have clinical utility in the treatment of non-small cell lung cancer (NSCLC) patients. Despite encouraging clinical efficacy with these agents, many patients develop resistance due to sensitizing (or activating) mutations ultimately leading to disease progression. In the majority of the cases, this resistance is due to the T790M mutation and frequently coexisting L858R. In addition, EGFR wild type receptor inhibition can lead to on target related dose limiting toxicities such as rash and diarrhea. We describe herein the identification of a mutant selective lead compound 12, an irreversible covalent inhibitor of EGFR T790M/L858R resistance mutations with selectivity over the wild type form. Significant tumor growth inhibition in preclinical models was observed with this lead. PubMed: 34624491DOI: 10.1016/j.bmcl.2021.128406 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.56 Å) |
Structure validation
Download full validation report
