School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China.
Central Laboratory, The First Hospital of Lanzhou University, Lanzhou 730000, China.
Biomolecules. 2023 Jun 14;13(6):988. doi: 10.3390/biom13060988.
Around 11% of all known gene lesions causing human genetic diseases are nonsense mutations that introduce a premature stop codon (PTC) into the protein-coding gene sequence. Drug-induced PTC readthrough is a promising therapeutic strategy for treating hereditary diseases caused by nonsense mutations. To date, it has been found that more than 50 small-molecular compounds can promote PTC readthrough, known as translational readthrough-inducing drugs (TRIDs), and can be divided into two major categories: aminoglycosides and non-aminoglycosides. This review summarizes the pharmacodynamics and clinical application potential of the main TRIDs discovered so far, especially some newly discovered TRIDs in the past decade. The discovery of these TRIDs brings hope for treating nonsense mutations in various genetic diseases. Further research is still needed to deeply understand the mechanism of eukaryotic cell termination and drug-induced PTC readthrough so that patients can achieve the greatest benefit from the various TRID treatments.
大约 11%的已知导致人类遗传疾病的基因病变是无义突变,这些突变会在蛋白质编码基因序列中引入过早终止密码子(PTC)。药物诱导的 PTC 通读是治疗无义突变引起的遗传性疾病的一种很有前途的治疗策略。迄今为止,已经发现超过 50 种小分子化合物可以促进 PTC 通读,称为翻译通读诱导药物(TRIDs),可分为两大类:氨基糖苷类和非氨基糖苷类。本文综述了迄今为止发现的主要 TRIDs 的药效学和临床应用潜力,特别是过去十年中发现的一些新的 TRIDs。这些 TRIDs 的发现为治疗各种遗传疾病中的无义突变带来了希望。仍需要进一步研究以深入了解真核细胞终止和药物诱导的 PTC 通读的机制,以便患者能够从各种 TRID 治疗中获得最大益处。