Microtubules, one of the cytoskeletons in eukaryotic cells, maintain the proper operation of several cellular functions. Additionally, they are regulated by the acetylation of HDAC6 and SIRT2 which affects microtubule dynamics. Given the fact that tubulin and HDAC inhibitors play a synergistic effect in the treatment of many cancers, the development of tubulin/HDAC dual-target inhibitors is conducive to addressing multiple limitations including drug resistance, dose toxicity, and unpredictable pharmacokinetic properties. At present, tubulin/HDAC dual-target inhibitors have been obtained in three main ways: uncleavable linked pharmacophores, cleavable linked pharmacophores, and modification of single-target drugs. Their therapeutic efficacy has been verified in vivo and in vitro assays. In this article, we reviewed the research progress of tubulin/HDAC dual inhibitors from design strategies, SARs, and biological activities, which may provide help for the discovery of novel tubulin/HDAC dual inhibitors.

中文翻译：

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微管蛋白/HDAC 双靶点抑制剂：来自设计策略、SAR 和治疗潜力的见解


微管是真核细胞中的细胞骨架之一，可维持多种细胞功能的正常运作。此外，它们受 HDAC6 和 SIRT2 乙酰化的调节，从而影响微管动力学。鉴于微管蛋白和 HDAC 抑制剂在许多癌症的治疗中发挥协同作用，微管蛋白/HDAC 双靶点抑制剂的开发有利于解决包括耐药性、剂量毒性和不可预测的药代动力学特性在内的多重限制。目前，微管蛋白/HDAC 双靶点抑制剂主要通过三种方式获得：不可切割的连接药效团、可切割的连接药效团和单靶点药物的修饰。它们的治疗效果已在体内和体外测定中得到验证。本文从设计策略、SARs和生物活性等方面综述了微管蛋白/HDAC双重抑制剂的研究进展，可能为新型微管蛋白/HDAC双重抑制剂的发现提供帮助。