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Review Article

多靶点HDAC抑制剂作为抗癌药物的现状和未来展望

卷 30, 期 24, 2023

发表于: 04 November, 2022

页: [2762 - 2795] 页: 34

弟呕挨: 10.2174/0929867329666220922105615

价格: $65

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摘要

多靶点药物可以依次与多个靶点相互作用，即使活性相对适度，也能对包括癌症在内的多种复杂疾病产生协同作用和更有效的治疗。组蛋白脱乙酰酶（HDAC）抑制剂是低分子量的小化合物，可增加组蛋白和非组蛋白的乙酰化，改变基因表达，从而影响血管生成、转移和细胞凋亡等过程。 HDAC 抑制剂影响多种细胞通路，从而产生不良问题，导致治疗耐药性，并且它们的药代动力学特性较差。设计基于 HDAC 的双/多靶点抑制剂是克服不良反应、耐药性和提高控制癌症有效性的重要策略。设计多靶点HDAC抑制剂的靶点组合选择一般是在系统高通量筛选（HTS）、网络药理学分析方法的基础上完成的。使用理性或计算方法执行药效团针对单个目标的识别。鉴定的药效团可以与可裂解或不可裂解的接头合并、融合或连接，以保留与原始靶标的相互作用，同时与其他靶标兼容。本综述的目的是阐明潜在靶标的设计策略、生物活性，以及作为潜在抗癌剂的双重/多靶点 HDAC 抑制剂的最新发展。本综述阐述了潜在靶标的设计策略以及生物活性，以及双/多靶点 HDAC 抑制剂作为潜在抗癌剂的最新发展。基于 HDAC 的双/多靶点抑制剂的开发对于克服副作用、耐药性和有效的癌症控制非常重要。

关键词: 组蛋白去乙酰酶，HDAC抑制剂，抗癌，双/多靶点，设计策略，计算方法，最新进展。

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