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  2. Study of the inhibitory effects on TNF-α-induced NF-κB activation of IMD0354 analogs

Study of the inhibitory effects on TNF-α-induced NF-κB activation of IMD0354 analogs

  • Chem Biol Drug Des. 2017 Dec;90(6):1307-1311. doi: 10.1111/cbdd.13032.
Yi-Rong Li 1 2 Chi-Chen Lin 2 Chih-Yuan Huang 1 Yung-Hao Wong 2 Cheng-Hung Hsieh 1 Han-Wei Wu 1 Jeremy J W Chen 2 Yu-Shan Wu 1
Affiliations

Affiliations

  • 1 Department of Chemistry, Tunghai University, Taichung, Taiwan.
  • 2 Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan.
Abstract

Nuclear factor-κB (NF-κB) is an important nuclear transcription factor which regulates pro-inflammatory cytokines such as TNF-α, IL-6. Its role as immunoregulatory mediator makes it an attractive target in the development of treatments for inflammatory and autoimmune diseases. In this study, we synthesized derivatives of IMD0354, a known inhibitor for NF-κB, in attempt to understand the effect of benzanilide substitutions on its activity. The inhibition of these analogs on NF-κB activation was analyzed by luciferase assay. The inhibition of IKKβ phosphorylation and pro-inflammatory cytokines was determined by Western blot and Real-Time PCR. The structure activity relationships showed that the hydroxyl group on IMD0354 is a critical moiety that resulting in the inhibition of NF-κB. Derivatives 1m, 2b, and 2c were shown to inhibit pro-inflammatory cytokine production at low concentration. These newly synthesized compounds may be useful for the treatment of chronic inflammatory disorders or for Cancer prevention.

Keywords

IL-6; IMD0354 analogs; NF-κB; TNF-α; benzanilide substitutions; chronic inflammatory.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-10172
    99.51%, IKKβ Inhibitor
    IKK