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Molecular Models02:00

Molecular Models

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Physical models representing molecular architectures of chemical compounds play essential roles in understanding chemistry. The use of molecular models makes it easier to visualize the structures and shapes of atoms and molecules.
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Related Experiment Video

Updated: Jan 17, 2026

Spatiotemporally Controlled Nuclear Translocation of Guests in Living Cells Using Caged Molecular Glues as Photoactivatable Tags
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Spatiotemporally Controlled Nuclear Translocation of Guests in Living Cells Using Caged Molecular Glues as Photoactivatable Tags

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A Complete Mechanistic Framework for Molecular Glue Characterization.

Maxime Couturier1, Ryan Guilbert1, Paul Clarkson1

  • 1Assays, Profiling & Cell Sciences, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge CB2 0AA, United Kingdom.

Journal of the American Chemical Society
|September 13, 2025
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Summary

Molecular glues offer a new way to target difficult diseases by altering protein interactions. Our new model precisely measures molecular glue properties, aiding drug discovery and development.

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Area of Science:

  • Biochemistry
  • Drug Discovery
  • Chemical Biology

Background:

  • Molecular glues are a novel therapeutic modality for modulating protein-protein interactions.
  • Targeting previously intractable proteins with small molecules is a significant challenge in drug discovery.
  • A lack of comprehensive theoretical frameworks hinders the development and application of molecular glues.

Purpose of the Study:

  • To establish a complete mechanistic analysis for determining molecular glue binding and cooperativity.
  • To provide a theoretical framework for understanding molecular glue mechanisms.
  • To facilitate the application of molecular glues in drug discovery.

Main Methods:

  • Developed a mechanistic analysis model.
  • Utilized a simple biochemical matrix experiment for data acquisition.
  • Validated the model using numerical integration.
  • Employed fluorescence resonance energy transfer (FRET) and fluorescence polarization assays.

Main Results:

  • The model accurately determines molecular glues' binding and cooperativity values.
  • All thermodynamic parameters of molecular glues can be determined.
  • Experimental validation confirmed the model's efficacy.

Conclusions:

  • The developed mechanistic analysis provides a robust theoretical framework for molecular glues.
  • This framework significantly aids in molecular glue optimization and characterization of neo-substrates.
  • The findings have broad implications for advancing drug discovery efforts utilizing molecular glues.