AI Article Synopsis
- EF24 is an IKKβ inhibitor with anti-tumor properties, and researchers designed and synthesized various analogs to find more effective alternatives.
- The most promising analog, named B3, exhibited a significantly improved inhibitory activity (IC: 6.6 μM) and effectively suppressed the growth of cancer cells like Hela229 and A549.
- B3 disrupted the NF-κB signaling pathway and induced cell cycle arrest and apoptosis in specific cancer cell lines, while also significantly reducing tumor growth in an animal model.
Article Abstract
EF24 is an IKKβ inhibitor (IC: 72 μM) containing various anti-tumor activities. In this study, a series of EF24 analogs targeting IKKβ were designed and synthesized. Several IKKβ inhibitors with better activities than EF24 were screened out and B3 showed best IKKβ inhibitory (IC: 6.6 μM). Molecular docking and dynamic simulation experiments further confirmed this inhibitory effect. B3 obviously suppressed the viability of Hela229, A549, SGC-7901 and MGC-803 cells. Then, in SGC-7901 and MGC-803 cells, B3 blocked the NF-κB signal pathway by inhibiting IKKβ phosphorylation, and followed arrested the cell cycle at G2/M phase by suppressing the Cyclin B1 and Cdc2 p34 expression, induced the cell apoptosis by down-regulating Bcl-2 protein and up-regulating cleaved-caspase3. Moreover, B3 significantly reduced tumor growth and suppressed the IKKβ-NF-κB signal pathway in SGC-7901 xenograft model. In total, this study present a potential IKKβ inhibitor as anti-tumor precursor.
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| http://dx.doi.org/10.1016/j.ejmech.2017.11.077 | DOI Listing |
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