INH14, a Small-Molecule Urea Derivative, Inhibits the IKKα/β-Dependent TLR Inflammatory Response.
drug discovery
inflammation
inhibitors
proteins
receptors
Journal
Chembiochem : a European journal of chemical biology
ISSN: 1439-7633
Titre abrégé: Chembiochem
Pays: Germany
ID NLM: 100937360
Informations de publication
Date de publication:
01 03 2019
01 03 2019
Historique:
received:
22
10
2018
pubmed:
18
11
2018
medline:
31
12
2019
entrez:
18
11
2018
Statut:
ppublish
Résumé
N-(4-Ethylphenyl)-N'-phenylurea (INH14) is a fragment-like compound that inhibits the toll-like receptor 2 (TLR2)-mediated inflammatory activity and other inflammatory pathways (i.e., TLR4, TNF-R and IL-1R). In this study, we determined the molecular target of INH14. Overexpression of proteins that are part of the TLR2 pathway in cells treated with INH14 indicated that the target lay downstream of the complex TAK1/TAB1. Immunoblot assays showed that INH14 decreased IkBα degradation in cells activated by lipopeptide (TLR2 ligand). These data indicated the kinases IKKα and/or IKKβ as the targets of INH14, which was confirmed with kinase assays (IC
Identifiants
pubmed: 30447158
doi: 10.1002/cbic.201800647
pmc: PMC6680106
doi:
Substances chimiques
NF-kappa B
0
Urea
8W8T17847W
I-kappa B Kinase
EC 2.7.11.10
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
710-717Subventions
Organisme : Austrian Science Fund FWF
ID : P 30779
Pays : Austria
Informations de copyright
© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
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