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抗疟药物发现中分子靶标的优先级排序。

Prioritization of Molecular Targets for Antimalarial Drug Discovery.

机构信息

Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, University of Dundee, Dundee, DD1 5EH, United Kingdom.

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

出版信息

ACS Infect Dis. 2021 Oct 8;7(10):2764-2776. doi: 10.1021/acsinfecdis.1c00322. Epub 2021 Sep 15.

Abstract

There is a shift in antimalarial drug discovery from phenotypic screening toward target-based approaches, as more potential drug targets are being validated in species. Given the high attrition rate and high cost of drug discovery, it is important to select the targets most likely to deliver progressible drug candidates. In this paper, we describe the criteria that we consider important for selecting targets for antimalarial drug discovery. We describe the analysis of a number of drug targets in the Malaria Drug Accelerator (MalDA) pipeline, which has allowed us to prioritize targets that are ready to enter the drug discovery process. This selection process has also highlighted where additional data are required to inform target progression or deprioritization of other targets. Finally, we comment on how additional drug targets may be identified.

摘要

抗疟药物研发正从表型筛选向基于靶点的方法转变,因为在 物种中越来越多的潜在药物靶点得到了验证。鉴于药物发现的高淘汰率和高成本,选择最有可能提供有进展潜力的候选药物的靶点非常重要。在本文中,我们描述了我们认为对抗疟药物研发中选择靶点很重要的标准。我们描述了对疟疾药物加速器(MalDA)管道中的一些药物靶点的分析,这使我们能够优先考虑那些准备进入药物发现过程的靶点。这一选择过程还突出了需要哪些额外的数据来告知目标进展或优先考虑其他目标。最后,我们评论了如何识别其他药物靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e2a/8608365/475ded12c884/id1c00322_0001.jpg

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