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Understanding insulin-like peptide 5 (INSL5) and relaxin family peptide receptor 4 (RXFP4): structure, signalling, and function.

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Related Experiment Video

Updated: Jan 12, 2026

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From Structure to Function: Development of Relaxin-3 Analogs and their Role in RXFP3 Signaling.

Isabelle Riches1, Hongkang Wu1, Predrag Kalaba1

  • 1Florey Department of Neuroscience and Mental Health, The University of Melbourne, Victoria, 3052, Australia.

Chembiochem : a European Journal of Chemical Biology
|November 8, 2025
PubMed
Summary
This summary is machine-generated.

Relaxin-3, a neuropeptide regulating feeding and stress, shows therapeutic potential. Advances in structural biology and chemistry enable the development of novel RXFP3-targeting drugs for various disorders.

Keywords:
G protein‐coupled receptorsRXFP3neuropeptide therapeuticspeptide engineeringrelaxin‐3

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Area of Science:

  • Neuroendocrinology
  • Structural Biology
  • Medicinal Chemistry

Background:

  • Relaxin-3 is a neuropeptide regulating feeding behavior, stress, arousal, addiction, and cognition.
  • The relaxin-3/RXFP3 signaling system is a key regulator of these physiological processes.
  • Recent structural studies have illuminated ligand-receptor interactions.

Purpose of the Study:

  • To review current knowledge of relaxin-3 structure, receptor interactions, and pharmacology.
  • To highlight the therapeutic potential of the relaxin-3/RXFP3 system.
  • To discuss advances enabling rational drug development for RXFP3-targeted therapeutics.

Main Methods:

  • Cryo-electron microscopy
  • Mutagenesis studies
  • Pharmacological studies
  • Peptide chemistry
  • Small-molecule design

Main Results:

  • Structural insights into RXFP3-ligand complexes have been obtained.
  • Diverse RXFP3 ligands, including analogs and small molecules, have been designed.
  • These tools aid in probing relaxin-3 biology and highlight therapeutic potential.

Conclusions:

  • The relaxin-3/RXFP3 system holds therapeutic promise for anxiety, depression, obesity, and substance use disorders.
  • Advances in structural biology and medicinal chemistry are crucial for developing RXFP3-targeted therapeutics.
  • Challenges in drug development include blood-brain barrier penetration and pharmacokinetic optimization.