Synthesis and biological activity of 2-cyanoacrylamide derivatives tethered to imidazopyridine as TAK1 inhibitors.
Acrylamide
/ chemistry
Binding Sites
Humans
Imidazoles
/ chemical synthesis
MAP Kinase Kinase Kinases
/ antagonists & inhibitors
Mercaptoethanol
/ chemistry
Models, Molecular
NF-kappa B
/ metabolism
Protein Binding
Protein Kinase Inhibitors
/ chemical synthesis
Pyridines
/ chemical synthesis
Signal Transduction
Structure-Activity Relationship
Transcription Factor RelA
Zearalenone
/ analogs & derivatives
2-cyanoacrylamide
TAK1
imidazopyridine
reversible covalent chemistry
small molecule inhibitor
Journal
Journal of enzyme inhibition and medicinal chemistry
ISSN: 1475-6374
Titre abrégé: J Enzyme Inhib Med Chem
Pays: England
ID NLM: 101150203
Informations de publication
Date de publication:
Dec 2020
Dec 2020
Historique:
entrez:
22
10
2020
pubmed:
23
10
2020
medline:
28
5
2021
Statut:
ppublish
Résumé
The importance of transforming growth factor beta-activated kinase 1 (TAK1) to cell survival has been demonstrated in many studies. TAK1 regulates signalling cascades, the NF-κB pathway and the mitogen-activated protein kinase (MAPK) pathway. TAK1 inhibitors can induce the apoptosis of cancerous cells, and irreversible inhibitors such as (5Z)-7-oxozeaenol are highly potent. However, they can react non-specifically with cysteine residues in proteins, which may have serious adverse effects. Reversible covalent inhibitors have been suggested as alternatives. We synthesised imidazopyridine derivatives as novel TAK1 inhibitors, which have 2-cyanoacrylamide moiety that can form reversible covalent bonding. A derivative with 2-cyano-3-(6-methylpyridin-2-yl)acrylamide (
Identifiants
pubmed: 33086897
doi: 10.1080/14756366.2020.1833876
pmc: PMC7594721
doi:
Substances chimiques
7-oxozeanol
0
Imidazoles
0
NF-kappa B
0
Protein Kinase Inhibitors
0
Pyridines
0
RELA protein, human
0
Transcription Factor RelA
0
imidazopyridine
0
Acrylamide
20R035KLCI
Zearalenone
5W827M159J
Mercaptoethanol
60-24-2
MAP Kinase Kinase Kinases
EC 2.7.11.25
MAP kinase kinase kinase 7
EC 2.7.11.25
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1928-1936Références
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