Refinement of Covalent EGFR Inhibitor AZD9291 to Eliminate Off-target Activity.
Journal
Tetrahedron letters
ISSN: 0040-4039
Titre abrégé: Tetrahedron Lett
Pays: England
ID NLM: 2984819R
Informations de publication
Date de publication:
22 Jun 2021
22 Jun 2021
Historique:
entrez:
12
11
2021
pubmed:
13
11
2021
medline:
13
11
2021
Statut:
ppublish
Résumé
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 analogues of AZD9291 by chemical proteomics, identifying analogues that maintain T790M-EGFR engagement while showing reduced cross-reactivity with off-targets.
Identifiants
pubmed: 34764521
doi: 10.1016/j.tetlet.2021.153178
pmc: PMC8577418
mid: NIHMS1703997
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : NCI NIH HHS
ID : R35 CA231991
Pays : United States
Déclaration de conflit d'intérêts
Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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