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Sculpting Cell Fate: The Expanding Universe of Nondegradative Proximity-Inducing Tools

Hangdi Xiao1, Lan Wang1, Mengxiao Chen1

  • 1School of Pharmacy, China Pharmaceutical University, Nanjing, China.

Chemmedchem
|February 12, 2026
PubMed

Insights

Nondegradative proximity-inducing chimeras offer new therapeutic strategies by modulating protein function without degradation. This review categorizes these novel agents into inhibition, stabilization, PTM, and cellular switches for broader applications.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Drug Discovery

Background:

  • Targeted therapy advancements include proximity-inducing chimeras like PROTACs.
  • Degradative approaches can cause toxicity, necessitating alternative strategies.
  • Nondegradative chimeras offer a safer alternative for modulating protein function.

Purpose of the Study:

  • To systematically categorize nondegradative proximity-inducing chimeras.
  • To elucidate the mechanisms of action for various nondegradative modalities.
  • To highlight emerging therapeutic applications beyond oncology.

Main Methods:

  • Literature review and synthesis of current research on nondegradative chimeras.
  • Categorization based on functional outcomes: targeted inhibition, stabilization, PTM, and cellular switches.
  • Analysis of representative technologies, including molecular glues.

Main Results:

  • Nondegradative chimeras are classified into four functional categories.
  • Mechanisms of action for each category are detailed.
  • Cutting-edge research and recent advancements are presented.

Conclusions:

  • Nondegradative chimeras represent a significant advancement in targeted therapy.
  • These modalities offer a unified mechanistic framework for diverse applications.
  • The field shows promise for novel therapeutic strategies beyond oncology.
Keywords:
chemical proximity‐inducedmolecular gluesnondegradativepost‐translational modificationproximity‐inducing chimeras

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