Optimizing the aryl-triazole of cjoc42 for enhanced gankyrin binding and anti-cancer activity.
Antineoplastic Agents
/ chemistry
Benzenesulfonates
/ chemistry
Binding Sites
Cell Line, Tumor
Cell Proliferation
/ drug effects
Drug Screening Assays, Antitumor
Humans
Molecular Dynamics Simulation
Proteasome Endopeptidase Complex
/ chemistry
Protein Binding
Proto-Oncogene Proteins
/ chemistry
Structure-Activity Relationship
Triazoles
/ chemistry
Antiproliferation
Breast cancer
Gankyrin
Liver cancer
Lung cancer
Protein-protein interactions
Journal
Bioorganic & medicinal chemistry letters
ISSN: 1464-3405
Titre abrégé: Bioorg Med Chem Lett
Pays: England
ID NLM: 9107377
Informations de publication
Date de publication:
01 09 2020
01 09 2020
Historique:
received:
03
04
2020
revised:
24
06
2020
accepted:
26
06
2020
entrez:
3
8
2020
pubmed:
3
8
2020
medline:
9
6
2021
Statut:
ppublish
Résumé
Gankyrin is an oncoprotein overexpressed in numerous cancer types and appears to play a key role in regulating cell proliferation, cell growth, and cell migration. These roles are largely due to gankyrin's protein-protein interaction with the 26S proteasome. We previously published a study exploring the aryl sulfonate ester of cjoc42 in an effort to enhance gankyrin binding and inhibit cancer cell proliferation. In order to further improve the gankyrin binding ability of the cjoc42 scaffold, an extensive SAR for the aryl-triazole moiety of cjoc42 was developed. Our cjoc42 derivatives exhibited enhanced gankyrin binding, as well as enhanced antiproliferative activity against Hep3B, HepG2, A549, and MDA-MB-231 cancer cell lines.
Identifiants
pubmed: 32738965
pii: S0960-894X(20)30483-2
doi: 10.1016/j.bmcl.2020.127372
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Benzenesulfonates
0
PSMD10 protein, human
0
Proto-Oncogene Proteins
0
Triazoles
0
cjoc42 compound
0
Proteasome Endopeptidase Complex
EC 3.4.25.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
127372Informations de copyright
Copyright © 2020 Elsevier Ltd. 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.