Refinement of Covalent EGFR Inhibitor AZD9291 to Eliminate Off-target Activity
| Autor: | Balyn W. Zaro, Elise Bouffard, Melissa M. Dix, Chi-Huey Wong, Benjamin F. Cravatt |
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| Rok vydání: | 2021 |
| Předmět: |
Side effect
010405 organic chemistry Chemistry Organic Chemistry Disease Drug resistance 010402 general chemistry Proteomics medicine.disease 01 natural sciences Biochemistry Article 0104 chemical sciences respiratory tract diseases T790M Drug Discovery medicine Cancer research Lung cancer Tyrosine kinase EGFR inhibitors |
| Zdroj: | Tetrahedron Lett |
| ISSN: | 0040-4039 |
| Popis: | Non-small-cell lung cancer (NSCLC) is a major disease that accounts for 85% of all lung cancer cases which claimed around 1.8 billion lives worldwide in 2020. Tyrosine kinase inhibitors (TKIs) that target EGFR have been used for the treatment of NSCLC, but often develop drug resistance, and the covalent inhibitor AZD9291 has been developed to tackle the problem of drug resistance mediated by the T790M EGFR mutation; however, there is a side effect of hyperglycemia that may be due to off-target activity. This study examines analogs of AZD9291 by chemical proteomics, identifying analogs that maintain T790M-EGFR engagement while showing reduced cross-reactivity with off-targets. |
| Databáze: | OpenAIRE |
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