Strategies for senolytic drug discovery.
cellular senescence
drug discovery
senescence
senolytics
Journal
Aging cell
ISSN: 1474-9726
Titre abrégé: Aging Cell
Pays: England
ID NLM: 101130839
Informations de publication
Date de publication:
10 2023
10 2023
Historique:
revised:
14
07
2023
received:
25
05
2023
accepted:
14
07
2023
medline:
23
10
2023
pubmed:
7
8
2023
entrez:
7
8
2023
Statut:
ppublish
Résumé
Senolytics are a category of drugs that reduce the impact of cellular senescence, an effect associated with a range of chronic and age-related diseases. Since the discovery of the first senolytics in 2015, the number of known senolytic agents has grown dramatically. This review discusses the broad categories of known senolytics-kinase inhibitors, Bcl-2 family protein inhibitors, naturally occurring polyphenols, heat shock protein inhibitors, BET family protein inhibitors, P53 stabilizers, repurposed anti-cancer drugs, cardiac steroids, PPAR-alpha agonists, and antibiotics. The approaches used to screen for new senolytics are articulated including a range of methods to induce senescence, different target cell types, various senolytic assays, and markers. The choice of methods can greatly influence the outcomes of a screen, with high-quality screens featuring robust systems, adequate controls, and extensive validation in alternate assays. Recent advances in single-cell analysis and computational methods for senolytic identification are also discussed. There is significant potential for further drug discovery, but this will require additional research into drug targets and mechanisms of actions and their subsequent rigorous evaluation in pre-clinical models and human trials.
Identifiants
pubmed: 37548098
doi: 10.1111/acel.13948
pmc: PMC10577556
doi:
Substances chimiques
Senotherapeutics
0
Antineoplastic Agents
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13948Informations de copyright
© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.
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