研究动态
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鱼类在药物发现中的应用: 一篇关于基于斑马鱼的分子筛选的综述。

Flight for fish in drug discovery: a review of zebrafish-based screening of molecules.

发表日期:2023 Aug
作者: Surjya Narayan Dash, Lipika Patnaik
来源: Disease Models & Mechanisms

摘要:

人类疾病和生物实践在斑马鱼(Danio rerio)中以药物开发的不同阶段以及毒性评估作为模型。斑马鱼在体内病理研究和疾病进程高分辨率研究方面具有理想特点。斑马鱼相比其他哺乳动物模型具有成本效益高,外部发育和胚胎透明,易于应用基因操作,并且适用于前向和逆向基因技术。斑马鱼药物筛选适用于靶点鉴定,疾病建模,高通量筛选抑制或预防疾病表型的化合物以及新药研发。最近进入临床或临床试验的几种药物源于斑马鱼。斑马鱼模型中使用的先进筛选方法预计将在推进药物开发项目中发挥重要作用。本综述重点介绍了药物发现过程中的最新进展,包括在疾病背景下理解药物的作用以及在神经疾病、心血管疾病、肾小球病和癌症方面筛选新的候选物的技术和方法。此外,它总结了选择小分子化合物和斑马鱼药物筛选测试执行的当前技术限制。
Human disease and biological practices are modelled in zebrafish (Danio rerio) at various phases of drug development as well as toxicity evaluation. The zebrafish is ideal for in vivo pathological research and high-resolution investigation of disease progress. Zebrafish has an advantage over other mammalian models, it is cost-effective, it has external development and embryo transparency, easy to apply genetic manipulations, and open to both forward and reverse genetic techniques. Drug screening in zebrafish is suitable for target identification, illness modelling, high-throughput screening of compounds for inhibition or prevention of disease phenotypes and developing new drugs. Several drugs that have recently entered the clinic or clinical trials have their origins in zebrafish. The sophisticated screening methods used in zebrafish models are expected to play a significant role in advancing drug development programmes. This review highlights the current developments in drug discovery processes, including understanding the action of drugs in the context of disease and screening novel candidates in neurological diseases, cardiovascular diseases, glomerulopathies and cancer. Additionally, it summarizes the current techniques and approaches for the selection of small molecules and current technical limitations on the execution of zebrafish drug screening tests.