Pyrazole-4-Carboxamide (YW2065): A Therapeutic Candidate for Colorectal Cancer via Dual Activities of Wnt/β-Catenin Signaling Inhibition and AMP-Activated Protein Kinase (AMPK) Activation.
AMP-Activated Protein Kinases
/ chemistry
Animals
Antineoplastic Agents
/ chemistry
Apoptosis
Cell Proliferation
Colonic Neoplasms
/ drug therapy
Female
Gene Expression Regulation, Neoplastic
/ drug effects
Humans
Male
Mice
Mice, Inbred C57BL
Mice, Nude
Phosphorylation
Pyrazoles
/ chemistry
Tumor Cells, Cultured
Wnt Signaling Pathway
/ drug effects
Xenograft Model Antitumor Assays
beta Catenin
/ antagonists & inhibitors
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:
26 12 2019
26 12 2019
Historique:
pubmed:
27
11
2019
medline:
23
6
2020
entrez:
27
11
2019
Statut:
ppublish
Résumé
Dysregulation of the Wnt/β-catenin signaling pathway has been widely recognized as a pathogenic mechanism for colorectal cancer (CRC). Although numerous Wnt inhibitors have been developed, they commonly suffer from toxicity and unintended effects. Moreover, concerns have been raised in targeting this pathway because of its critical roles in maintaining stem cells and regenerating tissues and organs. On the basis of the anthelmintic drug pyrvinium and previous lead FX1128, we have developed a compound YW2065 (
Identifiants
pubmed: 31769984
doi: 10.1021/acs.jmedchem.9b01252
doi:
Substances chimiques
Antineoplastic Agents
0
CTNNB1 protein, human
0
Pyrazoles
0
beta Catenin
0
AMP-Activated Protein Kinases
EC 2.7.11.31
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM