期刊
MECHANISMS OF AGEING AND DEVELOPMENT
卷 200, 期 -, 页码 -出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mad.2021.111587
关键词
Senescence; Senolytics; Aging; Drug screening; Prodrugs; PROTACs
资金
- NIH [RO1 AG063543-02S1, P01 AG043376, U19 AG056278, RO1 AG063543, P01 AG062413]
- Glenn Foundation for Medical Research Postdoctoral Fellowships in Aging Research
This review discusses the approaches to identify senolytics, including bioinformatic analysis, compound screening, and prodrug strategies. It also mentions ways to optimize the identified senolytics for better efficacy.
The demonstration in model organisms that cellular senescence drives aging and age-related diseases has led to widespread efforts to identify compounds able to selectively kill senescent cells, termed senolytics. Approaches used to identify senolytics include bioinformatic analysis of senescent cell anti-apoptotic pathways (SCAPs) for drug development and screening of drugs libraries on different senescent cell types in culture. Alternatively, cytotoxic compounds can be made specific to senescent cells through a prodrug strategy such as linking the compound to a galactose moiety where toxicity is activated by lysosomal beta-galactosidase. Identified senolytics can then be optimized through medicinal chemistry or linking to E3 targeting moieties to facilitate proteolysis of their targets. This review will provide an overview of approaches to identify senolytics and an update of the classes of senolytics identified to date.
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