Targeting DNA Repair in Tumor Cells via Inhibition of ERCC1-XPF.
DNA Repair
DNA, Neoplasm
/ drug effects
DNA-Binding Proteins
/ antagonists & inhibitors
Dose-Response Relationship, Drug
Drug Design
Endonucleases
/ antagonists & inhibitors
HCT116 Cells
Humans
Models, Molecular
Molecular Structure
Pyrimidines
/ chemical synthesis
Structure-Activity Relationship
Tumor Cells, Cultured
Journal
Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531
Informations de publication
Date de publication:
12 09 2019
12 09 2019
Historique:
pubmed:
2
8
2019
medline:
1
7
2020
entrez:
2
8
2019
Statut:
ppublish
Résumé
The ERCC1-XPF heterodimer is a 5'-3' structure-specific endonuclease, which plays an essential role in several DNA repair pathways in mammalian cells. ERCC1-XPF is primarily involved in the repair of chemically induced helix-distorting and bulky DNA lesions, such as cyclobutane pyrimidine dimers (CPDs), and DNA interstrand cross-links. Inhibition of ERCC1-XPF has been shown to potentiate cytotoxicity of platinum-based drugs and cyclophosphamide in cancer cells. In this study, the previously described ERCC1-XPF inhibitor 4-((6-chloro-2-methoxyacridin-9-yl)amino)-2-((4-methylpiperazin-1-yl)methyl)phenol (compound
Identifiants
pubmed: 31369707
doi: 10.1021/acs.jmedchem.9b00326
doi:
Substances chimiques
DNA, Neoplasm
0
DNA-Binding Proteins
0
Pyrimidines
0
xeroderma pigmentosum group F protein
0
ERCC1 protein, human
EC 3.1.-
Endonucleases
EC 3.1.-
pyrimidine
K8CXK5Q32L
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM