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抗疟耐药组学——寻找新的药物靶点及其作用模式。

The antimalarial resistome - finding new drug targets and their modes of action.

机构信息

Department of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, United States.

Department of Pediatrics, University of California, San Diego, School of Medicine, La Jolla, CA 92093, United States.

出版信息

Curr Opin Microbiol. 2020 Oct;57:49-55. doi: 10.1016/j.mib.2020.06.004. Epub 2020 Jul 15.

Abstract

To this day, malaria remains a global burden, affecting millions of people, especially those in sub-Saharan Africa and Asia. The rise of drug resistance to current antimalarial treatments, including artemisinin-based combination therapies, has made discovering new small molecule compounds with novel modes of action an urgent matter. The concerted effort to construct enormous compound libraries and develop high-throughput phenotypic screening assays to find compounds effective at specifically clearing malaria-causing Plasmodium parasites at any stage of the life cycle has provided many antimalarial prospects, but does not indicate their target or mode of action. Here, we review recent advances in antimalarial drug discovery efforts, focusing on the following 'omics' approaches in mode of action studies: IVIEWGA, CETSA, metabolomic profiling.

摘要

时至今日,疟疾仍然是全球的负担,影响着数以百万计的人,特别是撒哈拉以南非洲和亚洲的人们。目前抗疟药物(包括青蒿素联合疗法)的耐药性不断上升,这使得发现具有新型作用模式的新小分子化合物成为当务之急。人们齐心协力构建庞大的化合物库,并开发高通量表型筛选检测方法,以寻找在生命周期的任何阶段都能有效清除疟原虫的化合物,这为疟疾药物研发提供了许多前景,但并不能表明其作用靶点或作用模式。在这里,我们回顾了抗疟药物发现工作的最新进展,重点介绍了作用模式研究中的以下“组学”方法:IVIEWGA、CETSA、代谢组学分析。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c8b/7763834/e7f2bb60e15f/gr1.jpg

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