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Broadening the horizon: The promise of PROTACs in non-malignant disorders

Liping Fu1, Gongruixue Zeng2, Yu Cao3

  • 1Department of Pharmacy, Shaoxing TCM Hospital Affiliated to Zhejiang Chinese Medical University, Shaoxing, 312000, Zhejiang Province, China.

European Journal of Medicinal Chemistry
|January 17, 2026
PubMed

Insights

Proteolysis-targeting chimeras (PROTACs) offer a novel way to degrade disease-causing proteins. This review explores their expanding use beyond cancer into immune, metabolic, neurodegenerative, and infectious diseases.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Drug Discovery

Background:

  • Proteolysis-targeting chimeras (PROTACs) are an innovative therapeutic modality.
  • PROTACs leverage the ubiquitin-proteasome system (UPS) to induce targeted protein degradation.
  • This approach is effective against proteins previously considered undruggable.

Purpose of the Study:

  • To review recent advances in PROTAC applications for non-oncological diseases.
  • To evaluate the therapeutic potential and clinical prospects of PROTACs in immune, metabolic, neurodegenerative, and infectious disorders.
  • To offer new perspectives for expanding the therapeutic landscape of PROTAC technology.

Main Methods:

  • Systematic literature review of PROTAC applications in non-oncological diseases.
  • Analysis of preclinical and clinical data on PROTACs in various disease models.
  • Evaluation of the mechanism of action and therapeutic efficacy of PROTACs.

Main Results:

  • PROTACs demonstrate significant therapeutic potential in immune, metabolic, neurodegenerative, and infectious diseases.
  • Early clinical studies show promise, with ongoing trials expanding the scope of application.
  • The review highlights successful degradation of target proteins across diverse non-oncological conditions.

Conclusions:

  • PROTACs represent a promising therapeutic strategy beyond oncology.
  • Further research and clinical development are warranted to fully realize the potential of PROTACs in treating a wide range of diseases.
  • PROTAC technology is poised to expand the therapeutic options for numerous unmet medical needs.
Keywords:
Immune diseasesNeurodegenerative diseasesPROTACTargeted protein degradation

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