ReviewChembiochem : a European journal of chemical biology2024
Senolytic Prodrugs: A Promising Approach to Enhancing Senescence-Targeting Intervention.
Review in Chembiochem : a European journal of chemical biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed.
- Orthogonal Light- and Enzyme-Triggered and-Gate Prodrugs for Senolytic Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- Precision-Engineered PROTACs: Integrating Physical and Chemical Strategies for Targeted Cancer Therapy.Small (Weinheim an der Bergstrasse, Germany) · 2026Review
- Modular Molecular Design and Self-Assembled Nanostructures of Saccharide‑Appended Cyclic Dipeptides for Glycosidase‑Responsive Supramolecular Hydrogels.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Decoding Senescence-Driven Heterogeneity in Early-Onset Colorectal Cancer for Prognostic and Therapeutic Stratification.Cancer science · 2026Article
- Cellular senescence and metabolic aging in type 2 diabetes: mechanistic insights and translational implications.Frontiers in endocrinology · 2026Review
- Telomerase-mediated immortalization preserves the anti-inflammatory activity of dental pulp stem cell extracellular vesicles.Frontiers in immunology · 2026Article
- Senescence of dental pulp stem cells: phenotypes, underlying mechanisms and regulatory molecules.Human cell · 2025Review
- Species-selective activation of a β-galactosidase fluorogenic probe.Scientific reports · 2025Article
- Targeting Ferroptosis to Eliminate Senescent Cells: Mechanisms and Therapeutic Potential.Aging and disease · 2025Review
- Targeting Senescence: A Review of Senolytics and Senomorphics in Anti-Aging Interventions.Biomolecules · 2025Review
- Ouabain - a double-edged sword in tumor development and progression? a review of half a century.Frontiers in physiology · 2025Review
- New insights into the role of cellular senescence and rheumatic diseases.Frontiers in immunology · 2025Review
- Development of Calcium-Dependent Phospholipase A2 Inhibitors to Target Cellular Senescence and Oxidative Stress in Neurodegenerative Diseases.Antioxidants & redox signaling · 2024Review
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Cellular senescence has emerged as a potential therapeutic target for aging and a wide range of age-related disorders. Despite the encouraging therapeutic impact of senolytic agents on improving lifespan and the outcomes of pharmacological intervention, the senolytic induced side effects pose barriers to clinical application. There is a pressing need for selective ablation of senescent cells (SnCs). The design of senolytic prodrugs has been demonstrated as a promising approach to addressing these issues. These prodrugs are generally designed via modification of senolytics with a cleavable galactose moiety to respond to the senescent biomarker - senescence-associated β-galactosidase (SA-β-gal) to restore their therapeutic effects. In this Concept, we summarize the developments by categorizing these prodrugs into two classes: 1) galactose-modified senolytic prodrugs, in which sensing unit galactose is either directly conjugated to the drug or via a self-immolative linker and 2) bioorthogonal activation of senolytic prodrugs. In the bioorthogonal prodrug design, galactose is incorporated into dihydrotetrazine to sense SA-β-gal for click activation. Notably, in addition to repurposed chemotherapeutics and small molecule inhibitors, PROTACs and photodynamic therapy have been introduced as new senolytics in the prodrug design. It is expected that the senolytic prodrugs would facilitate translating small-molecule senolytics into clinical use.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.