5J9Z
EGFR-T790M in complex with pyrazolopyrimidine inhibitor 1a
Summary for 5J9Z
| Entry DOI | 10.2210/pdb5j9z/pdb |
| Descriptor | Epidermal growth factor receptor, (R)-1-(3-(4-amino-3-(1-methyl-1H-indol-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one (3 entities in total) |
| Functional Keywords | tyrosine kinase, covalent inhibitor, drug resistance, transferase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 37550.50 |
| Authors | Becker, C.,Engel, J.,Rauh, D. (deposition date: 2016-04-11, release date: 2016-08-17, Last modification date: 2024-10-23) |
| Primary citation | Engel, J.,Becker, C.,Lategahn, J.,Keul, M.,Ketzer, J.,Muhlenberg, T.,Kollipara, L.,Schultz-Fademrecht, C.,Zahedi, R.P.,Bauer, S.,Rauh, D. Insight into the Inhibition of Drug-Resistant Mutants of the Receptor Tyrosine Kinase EGFR. Angew.Chem.Int.Ed.Engl., 55:10909-10912, 2016 Cited by PubMed Abstract: Targeting acquired drug resistance represents the major challenge in the treatment of EGFR-driven non-small-cell lung cancer (NSCLC). Herein, we describe the structure-based design, synthesis, and biological evaluation of a novel class of covalent EGFR inhibitors that exhibit excellent inhibition of EGFR-mutant drug-resistant cells. Protein X-ray crystallography combined with detailed kinetic studies led to a deeper understanding of the mode of inhibition of EGFR-T790M and provided insight into the key principles for effective inhibition of the recently discovered tertiary mutation at EGFR-C797S. PubMed: 27496389DOI: 10.1002/anie.201605011 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.5 Å) |
Structure validation
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