Discovery of potent small molecule PROTACs targeting mutant EGFR.
Adaptor Proteins, Signal Transducing
/ metabolism
Antineoplastic Agents
/ chemical synthesis
Apoptosis
/ drug effects
Autophagy
/ drug effects
Cell Line, Tumor
Cell Proliferation
/ drug effects
Drug Design
Drug Screening Assays, Antitumor
ErbB Receptors
/ antagonists & inhibitors
G1 Phase Cell Cycle Checkpoints
/ drug effects
Humans
Lenalidomide
/ analogs & derivatives
Protein Kinase Inhibitors
/ chemical synthesis
Proteolysis
/ drug effects
Purines
/ chemical synthesis
Ubiquitin-Protein Ligases
/ metabolism
Ubiquitination
/ drug effects
Von Hippel-Lindau Tumor Suppressor Protein
/ metabolism
Autophagy
Degradation
EGFR
PROTAC
Journal
European journal of medicinal chemistry
ISSN: 1768-3254
Titre abrégé: Eur J Med Chem
Pays: France
ID NLM: 0420510
Informations de publication
Date de publication:
15 Dec 2020
15 Dec 2020
Historique:
received:
25
07
2020
revised:
20
08
2020
accepted:
21
08
2020
pubmed:
5
9
2020
medline:
27
5
2021
entrez:
5
9
2020
Statut:
ppublish
Résumé
Epidermal growth factor receptor (EGFR) is an important therapeutic target for the treatment of non-small cell lung cancer. A number of efficacious EGFR tyrosine kinase inhibitors have been developed. However, acquired drug resistance largely encumbered their clinical practicability. Therefore, there is an urgent need to develop new therapeutic regime. Herein, we designed and synthesized a set of EGFR-targeting small molecule PROTACs which showed promising efficacy. In particular, VHL-recruiting compound P3 showed potent anti-proliferative activity against HCC827 and H1975 cell lines with IC
Identifiants
pubmed: 32883633
pii: S0223-5234(20)30753-4
doi: 10.1016/j.ejmech.2020.112781
pii:
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Antineoplastic Agents
0
CRBN protein, human
0
Protein Kinase Inhibitors
0
Purines
0
Ubiquitin-Protein Ligases
EC 2.3.2.27
Von Hippel-Lindau Tumor Suppressor Protein
EC 2.3.2.27
EGFR protein, human
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
VHL protein, human
EC 6.3.2.-
Lenalidomide
F0P408N6V4
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
112781Informations de copyright
Copyright © 2020 Elsevier Masson SAS. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest 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.