Developing INSL5 analogs as colon motility regulator

There are over 16% of people in the general population, and 32.5% of people aged 60-110, who are affected by chronic colon motility disorders due to decreased colonic propulsion (constipation) or increased propulsion (diarrhoea). It’s expected that the prevalence of chronic colon motility disorders will continue to rise as the population ages.

Current therapies to treat constipation and diarrhoea are inefficient and/or have adverse side effects; it’s clear that new approaches and targets are required to advance gastrointestinal motility pharmacotherapy.

In this project we’ll design and develop novel analogues of INSL5 as potential drug leads using modern solid phase peptide synthesis (SPPS). All analogues will be analysed, purified and characterised by a wide range of scientific techniques such as RP-HPLC, MALDI-TOF mass spectrometry, circular dichroism spectroscopy and nuclear magnetic resonance studies. All these analogues developed by various cutting-edge chemical approaches will also be screened using cell based (RXFP4) assays to test their binding and activity (e.g. competition binding assays and cAMP assays).

Further, the lead agonists and antagonists from pharmacological studies will be forwarded to the in vivo testing. The lead antagonists will be tested in animal models of diarrhoea, and agonists will be tested in animal models of constipation.