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Prodrugs are a class of pharmaceutical compounds that undergo a biotransformation process within the body to be converted into a pharmacologically active drug. Prodrugs are designed to improve the therapeutic properties of the parent drug, such as enhancing bioavailability, increasing stability, or reducing toxicity. The concept of prodrugs revolves around modifying the chemical structure of the original drug to make it more effective or convenient for administration.
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Related Experiment Video

Updated: Jun 19, 2025

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Senolytic Prodrugs: A Promising Approach to Enhancing Senescence-Targeting Intervention.

Mengyang Chang1, Yue Dong2, Alexis B Cruickshank-Taylor2

  • 1Department of Chemistry and Biochemistry, University of Arizona, Tucson, Arizona, 85721, USA.

Chembiochem : a European Journal of Chemical Biology
|July 26, 2024
PubMed
Summary

Senolytic prodrugs selectively eliminate senescent cells by utilizing galactose to activate drugs in response to senescence-associated β-galactosidase (SA-β-gal). This approach aims to minimize side effects and advance aging therapies.

Keywords:
PROTACProdrugsSenescenceSenescence-associated β-galactosidaseSenolytics

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Area of Science:

  • Biomedical Sciences
  • Gerontology
  • Drug Development

Background:

  • Cellular senescence is a therapeutic target for aging and age-related diseases.
  • Senolytic agents show promise but have side effects limiting clinical use.
  • Selective ablation of senescent cells (SnCs) is needed.

Purpose of the Study:

  • To review senolytic prodrug designs for selective SnC ablation.
  • To categorize prodrugs based on activation mechanisms.
  • To highlight advancements in senolytic prodrug development.

Main Methods:

  • Categorization of prodrugs into galactose-modified and bioorthogonal activation classes.
  • Description of galactose moiety conjugation and self-immolative linkers.
  • Explanation of bioorthogonal prodrugs using dihydrotetrazine for SA-β-gal sensing.

Main Results:

  • Senolytic prodrugs are designed to be activated by senescence-associated β-galactosidase (SA-β-gal).
  • Two main classes of prodrugs are identified: galactose-modified and bioorthogonal.
  • New senolytics like PROTACs and photodynamic therapy are incorporated into prodrug designs.

Conclusions:

  • Senolytic prodrugs offer a promising strategy to overcome side effects of current senolytics.
  • Prodrug design enables targeted delivery and activation, enhancing therapeutic potential.
  • These advancements are expected to facilitate the clinical translation of senolytic therapies.