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药物发现:无脊椎动物秀丽隐杆线虫的启示。

Drug discovery: Insights from the invertebrate Caenorhabditis elegans.

机构信息

Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB) CCT UNS-CONICET, Bahía Blanca, Argentina.

Dpto de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, Bahía Blanca, Argentina.

出版信息

Pharmacol Res Perspect. 2021 Apr;9(2):e00721. doi: 10.1002/prp2.721.

DOI:10.1002/prp2.721
PMID:33641258
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7916527/
Abstract

Therapeutic drug development is a long, expensive, and complex process that usually takes 12-15 years. In the early phases of drug discovery, in particular, there is a growing need for animal models that ensure the reduction in both cost and time. Caenorhabditis elegans has been traditionally used to address fundamental aspects of key biological processes, such as apoptosis, aging, and gene expression regulation. During the last decade, with the advent of large-scale platforms for screenings, this invertebrate has also emerged as an essential tool in the pharmaceutical research industry to identify novel drugs and drug targets. In this review, we discuss the reasons why C. elegans has been positioned as an outstanding cost-effective option for drug discovery, highlighting both the advantages and drawbacks of this model. Particular attention is paid to the suitability of this nematode in large-scale genetic and pharmacological screenings. High-throughput screenings in C. elegans have indeed contributed to the breakthrough of a wide variety of candidate compounds involved in extensive fields including neurodegeneration, pathogen infections and metabolic disorders. The versatility of this nematode, which enables its instrumentation as a model of human diseases, is another attribute also herein underscored. As illustrative examples, we discuss the utility of C. elegans models of both human neurodegenerative diseases and parasitic nematodes in the drug discovery industry. Summing up, this review aims to demonstrate the impact of C. elegans models on the drug discovery pipeline.

摘要

治疗药物的开发是一个漫长、昂贵且复杂的过程,通常需要 12-15 年。特别是在药物发现的早期阶段,越来越需要能够降低成本和时间的动物模型。秀丽隐杆线虫传统上用于解决凋亡、衰老和基因表达调控等关键生物学过程的基本方面。在过去的十年中,随着大规模筛选平台的出现,这种无脊椎动物也已成为制药研究行业中识别新型药物和药物靶点的重要工具。在这篇综述中,我们讨论了秀丽隐杆线虫为何被定位为具有成本效益的药物发现的杰出选择,强调了这种模型的优缺点。特别关注这种线虫在大规模遗传和药理学筛选中的适用性。秀丽隐杆线虫的高通量筛选确实促成了广泛领域涉及神经退行性疾病、病原体感染和代谢紊乱的候选化合物的突破。这种线虫的多功能性使其能够作为人类疾病的模型,这也是本文强调的另一个属性。作为说明性示例,我们讨论了秀丽隐杆线虫的人类神经退行性疾病和寄生线虫模型在药物发现行业中的应用。总之,本篇综述旨在展示秀丽隐杆线虫模型对药物发现管道的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a7c/7916527/dfad5096956a/PRP2-9-e00721-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a7c/7916527/dfad5096956a/PRP2-9-e00721-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a7c/7916527/dfad5096956a/PRP2-9-e00721-g001.jpg

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Cell Rep. 2022 Jan 25;38(4):110195. doi: 10.1016/j.celrep.2021.110195.
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Novel Immune Modulators Enhance Resistance to Multiple Pathogens.新型免疫调节剂增强对多种病原体的抵抗力。
mSphere. 2021 Jan 6;6(1):e00950-20. doi: 10.1128/mSphere.00950-20.
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Revealing the anticancer potential of candidate drugs in vivo using Caenorhabditis elegans mutant strains.
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Geroscience. 2025 Apr 3. doi: 10.1007/s11357-025-01627-4.
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Versatility of Caenorhabditis elegans as a Model Organism for Evaluating Foodborne Neurotoxins and Food Bioactive Compounds in Nutritional Neuroscience.秀丽隐杆线虫作为评估营养神经科学中食源神经毒素和食物生物活性化合物的模式生物的多功能性。
Mol Neurobiol. 2025 Jun;62(6):7205-7229. doi: 10.1007/s12035-025-04705-y. Epub 2025 Jan 25.
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Discovery of Human PIM Kinase Inhibitors as a Class of Anthelmintic Drugs to Treat Intestinal Nematode Infections.发现人类PIM激酶抑制剂作为一类治疗肠道线虫感染的抗蠕虫药物。
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