寻找创新药物的有效途径是通过研究天然产物，因为它们具有复杂且多变的结构以及多种生物活性。IKKβ（抑制ΚB激酶β），也被称为IKK2，是一个关键的调控性激酶，负责通过对其在Ser177和Ser181处的磷酸化，促进ΚB抑制因子（IκBs）的磷酸化，触发它们的泛素化和降解从而激活核因子κB（NF-κB）级联反应。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。在本综述中，我们总结了IKKβ的结构特征和传导机制，以及天然资源（如倍半萜类、二萜类、三萜类、黄酮类和生物碱）和化学合成（如嘧啶类、吡啶类、吡嗪类、喹啉类、噻吩类和噻唑烷类）中的抑制剂的发现。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。本综述将为基于天然产物或化学合成骨架的IKKβ抑制剂的结构修饰以及进一步的植物化学研究提供灵感。©作者。

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.© The author(s).