<br>IκB 激酶 β (IKKβ)：结构、转导机制、生物学功能及其抑制剂的发现。,International Journal of Biological Sciences

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IκB 激酶 β (IKKβ)：结构、转导机制、生物学功能及其抑制剂的发现。
International Journal of Biological Sciences ( IF 8.2 ) Pub Date : 2023-08-06 , DOI: 10.7150/ijbs.85158
Juan Zhang _{1,

2,

3} , Rui Zhang ₁ , Wei Li _{1,

4} , Xiao-Chi Ma ₂ , Feng Qiu ₁ , Cheng-Peng Sun _{1,

2}

Affiliation

由于天然产物的结构复杂多变，具有多种生物活性，因此发现创新药物的有效途径将向天然产物寻求答案。抑制性 kappa B 激酶 beta (IKKβ)，称为 IKK2，是一种关键的调节激酶，通过其 Ser177 和 Ser181 磷酸化来激活 NF-κB，从而促进 kappa B 抑制剂 (IκB) 的磷酸化，触发其泛素化和降解以激活核因子 kappa-B (NF-κB) 级联。化学抑制IKKβ或其基因敲除已成为阻断NF-κB介导的肿瘤细胞增殖和迁移以及炎症反应的有效方法。在这篇综述中，我们总结了IKKβ的结构特征和转导机制，以及从自然资源（如倍半萜类、二萜类、三萜类、黄酮类和生物碱类）和化学合成类（如嘧啶类、吡啶类、吡嗪类、喹喔啉类、噻吩类、和噻唑烷）。此外，还讨论了新型天然IKKβ抑制剂的生物合成途径及其生物学潜力。该综述将为基于天然产物骨架或化学合成的IKKβ抑制剂的结构修饰以及进一步的植物化学研究提供启发。

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IκB kinase β (IKKβ): Structure, transduction mechanism, biological function, and discovery of its inhibitors.

The effective approach to discover innovative drugs will ask natural products for answers because of their complex and changeable structures and multiple biological activities. Inhibitory kappa B kinase beta (IKKβ), known as IKK2, is a key regulatory kinase responsible for the activation of NF-κB through its phosphorylation at Ser177 and Ser181 to promote the phosphorylation of inhibitors of kappa B (IκBs), triggering their ubiquitination and degradation to active the nuclear factor kappa-B (NF-κB) cascade. Chemical inhibition of IKKβ or its genetic knockout has become an effective method to block NF-κB-mediated proliferation and migration of tumor cells and inflammatory response. In this review, we summarized the structural feature and transduction mechanism of IKKβ and the discovery of inhibitors from natural resources (e.g. sesquiterpenoids, diterpenoids, triterpenoids, flavonoids, and alkaloids) and chemical synthesis (e.g. pyrimidines, pyridines, pyrazines, quinoxalines, thiophenes, and thiazolidines). In addition, the biosynthetic pathway of novel natural IKKβ inhibitors and their biological potentials were discussed. This review will provide inspiration for the structural modification of IKKβ inhibitors based on the skeleton of natural products or chemical synthesis and further phytochemistry investigations.

更新日期：2023-08-06

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