Nuclear factor-κB mediated inhibition of cytokine production by imidazoline scaffolds
The mammalian nuclear transcription factor NF-κB is responsible for the transcription of multiple cytokines, including the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). Elevated levels of pro-inflammatory cytokines play an important role in the pathogenesis of inflammatory disorders such as rheumatoid arthritis (RA). Inhibition of the pro-inflammatory transcription factor NF-κB has therefore been identified as a possible therapeutic treatment for RA. We describe herein the synthesis and biological activity of a series of imidazoline-based scaffolds as potent inhibitors of NF-κB mediated gene transcription in cell culture as well as inhibitors of TNF-α and IL-6 production in interleukin 1 beta (IL-1β) stimulated human blood.
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Kahlon, D. K., Lansdell, T. A., Fisk, J. S., Hupp, C. D., Friebe, T. L., Hovde, S., … Tepe, J. J. (2009). Nuclear factor-κB mediated inhibition of cytokine production by imidazoline scaffolds. Journal of Medicinal Chemistry, 52(5), 1302–1309. doi:10.1021/jm8013162