Selective Covalent Targeting of Mutated EGFR(T790M) with Chlorofluoroacetamide-Pyrimidines.
Journal
ACS medicinal chemistry letters
ISSN: 1948-5875
Titre abrégé: ACS Med Chem Lett
Pays: United States
ID NLM: 101521073
Informations de publication
Date de publication:
11 Jun 2020
11 Jun 2020
Historique:
received:
04
12
2019
accepted:
08
04
2020
entrez:
20
6
2020
pubmed:
20
6
2020
medline:
20
6
2020
Statut:
epublish
Résumé
Covalent modification of disease-associated proteins with small molecules is a powerful approach for achieving an increased and sustained pharmacological effect. To reduce the potential risk of nonselective covalent modification, molecular design of covalent inhibitors is critically important. We report herein the development of a targeted covalent inhibitor for mutated epidermal growth factor receptor (EGFR) (L858R/T790M) using α-chlorofluoroacetamide (CFA) as the reactive group. The chemically tuned weak reactivity of CFA was suitable for the design of third-generation EGFR inhibitors that possess the pyrimidine scaffold. The structure-activity relationship study revealed that CFA inhibitor
Identifiants
pubmed: 32550993
doi: 10.1021/acsmedchemlett.9b00574
pmc: PMC7294701
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1137-1144Informations de copyright
Copyright © 2020 American Chemical Society.
Déclaration de conflit d'intérêts
The authors declare no competing financial interest.
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