Recent advances in the discovery of senolytics

Lei Zhang, Louise E. Pitcher, Vaishali Prahalad, Laura J. Niedernhofer, Paul D. Robbins

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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 β-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.

Original languageEnglish (US)
Article number111587
JournalMechanisms of Ageing and Development
Volume200
DOIs
StatePublished - Dec 2021

Bibliographical note

Funding Information:
This work was supported by NIH grants RO1 AG063543-02S1 , P01 AG043376 , U19 AG056278 , RO1 AG063543 , P01 AG062413 and the Glenn Foundation for Medical Research Postdoctoral Fellowships in Aging Research .

Publisher Copyright:
© 2021

Keywords

  • Aging
  • Drug screening
  • PROTACs
  • Prodrugs
  • Senescence
  • Senolytics

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