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Continuing challenges in targeting oligomeric GPCR-based drugs

Joaquin Botta1, Julia Appelhans1, Peter J McCormick1

  • 1Centre for Endocrinology, William Harvey Research Institute, Bart's and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.

Progress in Molecular Biology and Translational Science
|January 19, 2020
PubMed

Insights

Oligomeric G protein-coupled receptor (GPCR) structures show therapeutic promise. Understanding their mechanisms and challenges is key for developing new drug treatments.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Structural Biology

Background:

  • G protein-coupled receptors (GPCRs) are crucial drug targets.
  • The oligomeric nature of GPCRs is increasingly recognized.
  • Oligomeric complexes influence receptor function and signaling.

Purpose of the Study:

  • To explore the therapeutic potential of oligomeric GPCR structures.
  • To review the history and therapeutic relevance of these complexes.
  • To discuss drug targeting strategies for oligomeric GPCRs.

Main Methods:

  • Literature review of GPCR oligomerization studies.
  • Analysis of therapeutic and theranostic opportunities.
  • Examination of oligomer-specific modulation mechanisms.

Main Results:

  • Several examples of therapeutically relevant GPCR oligomers identified.
  • Mechanisms by which oligomers modulate GPCR function elucidated.
  • Challenges in targeting GPCR oligomers highlighted.

Conclusions:

  • Oligomeric GPCR structures represent a significant area for therapeutic intervention.
  • Targeting these complexes offers novel drug development avenues.
  • Overcoming challenges in oligomer-specific targeting is crucial for future treatments.
Keywords:
Bivalent ligandsG protein-coupled oligomersGPCR cross-talkGPCR homomersHeteromersInterference peptides

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