| Summary: | 碩士 === 東海大學 === 化學系 === 103 === NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) is a protein complex that controls transcription of DNA. When it is activated excessively, enhanced expression of pro-inflammatory cytokines such as TNF-α, lead to inflammatory and autoimmune diseases. The target was IKKβ, which play an key role in NF-κB signal pathway. We selected WY5107, which was designed from our Lab and has good inhibitory activity of IKKβ. In order to achieve better IKKβ inhibitory activity, we synthesis different bridges link WY5107 and another IKKβ inhibitor, IMD-0354, as a small-molecule, ATP-competitive inhibitor selectively targeting IKKβ kinase activity. And with the results of biological experiment, within all analogs synthesiszed, compound ( 8 ) exhibited the best IKKβ inhibitory activity. The SAR results showed that amino acids near the tetracyclic compounds which can form hydrophobic interaction, and the compounds modified by amine bridge exhibited better IKKβ
inhibitory activity than amide bridged analogs.
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