INH14, a Small-Molecule Urea Derivative, Inhibits the IKKα/β-Dependent TLR Inflammatory Response.

ABSTRACT: 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 (IC₅₀ IKKα=8.97 μm; IC₅₀ IKKβ=3.59 μm). Furthermore, in vivo experiments showed that INH14 decreased TNFα formed after lipopepti

SUBMITTER: Drexel M 

PROVIDER: S-EPMC6680106 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature