创新链/学科链/研发链/产业链

新药研发前沿动态 / 医药领域趋势进展

李根, 宁香丽, 李国菠. 靶向金属酶的金属结合药效特征研究进展[J]. 药学进展, 2020, 44(9): 667-680.
引用本文: 李根, 宁香丽, 李国菠. 靶向金属酶的金属结合药效特征研究进展[J]. 药学进展, 2020, 44(9): 667-680.
Gen Li, Ning Xiangli, Li Guobo. Recent Advances in Metal Binding Pharmacophores Targeting Metalloenzymes[J]. Progress in Pharmaceutical Sciences, 2020, 44(9): 667-680.
Citation: Gen Li, Ning Xiangli, Li Guobo. Recent Advances in Metal Binding Pharmacophores Targeting Metalloenzymes[J]. Progress in Pharmaceutical Sciences, 2020, 44(9): 667-680.

靶向金属酶的金属结合药效特征研究进展

Recent Advances in Metal Binding Pharmacophores Targeting Metalloenzymes

  • 摘要: 金属酶广泛存在于各种生物体,与人类疾病发生发展密切相关,是一大类重要的药物作用靶标。尽管已有若干靶向金属酶抑制剂批准用于临床,但大多数金属酶还缺乏特异性药物分子或尚未开发,靶向金属酶的创新药物研究仍然是目前重要领域之一。鉴于金属酶活性位点含金属离子的特殊性,金属酶抑制剂通常包含与活性位点金属离子形成配位的金属结合药效特征(MBP)。通过对挖掘的MBP数据进行归类总结,列举部分经典与少见的MBP类型,并分析对金属酶的选择性和杂泛性,期望能为靶向金属酶的创新药物研究提供线索和借鉴。

     

    Abstract: Metalloenzymes are widely distributed in a variety of organisms, and closely related with human diseases, which hence are considered as a wide range of important drug targets. Although several inhibitors targeting metalloenzymes have been approved for clinical use, there are a lack of drug candidates or high-quality inhibitors for most metalloenzymes, of which even many have not been exploited. Discovery of novel drugs targeting metalloenzymes is still one of important fields. Due to the distinctiveness of metal ions-containing active sites of metalloenzymes, the metalloenzyme inhibitors often bear a specific chemical moiety that is positioned to coordinate with active site metal ions, which is termed metal-binding pharmacophore (MBP). This review summarized the MBP data extracted from metalloenzyme-ligand interaction analyses, enumerated some classic MBPs, and analyzed the metalloenzyme selectivity and promiscuity. These information will provide clues and references for future innovative drug discovery targeting metalloenzymes.

     

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