New class of cyclophilin inhibitors shows promise for treatment of fatty liver disease

A new paper from an interdisciplinary Edinburgh team and collaborating biotech companies shows the promise of a new class of cyclophilin inhibitors as a much-needed additional treatment for MASH liver disease.

Metabolic dysfunction-associated steatohepatitis (MASH) liver disease is an increasingly prevalent condition characterized by inflammation and fibrosis of the liver caused by excess fat in cells. According to estimates, over one in ten adults in the UK suffer from MASH. Despite intense research efforts, only one drug has been approved to date for treating MASH, and it is effective in only one in four patients.

Now, a team of scientists from the University of Edinburgh - based at the School of Chemistry, the School of Biological Sciences, the Centre for Cardiovascular Sciences, and the Institute for Regeneration and Repair - have collaborated with the companies BioAscent, Cytochroma, Concept Life Sciences and Eurofins to discover a new class of small molecules that show promising potential for clearing fat build-up in cellular models of MASH disease.

Left: Study coordinators Prof. Alison Hulme, Dr Dahlia Doughty-Shenton and Prof. Julien Michel at the Joseph Black Building's historic main entrance; Right: Molecular dynamics simulation of the team's pyclophilin B inhibitor.
Left: Study coordinators Prof. Alison Hulme, Dr Dahlia Doughty-Shenton and Prof. Julien Michel; Right: Molecular dynamics simulation of the team's cyclophilin B inhibitor.

The work was coordinated by Dr. Dahlia Doughty-Shenton  - Edinburgh Innovations Fellow, Alison Hulme  - Professor of Synthesis and Chemical Biology, and Julien Michel – Professor of Biomolecular Simulation. Industrial collaborators provided access to expertise in synthetic medicinal chemistry, cellular assays and preclinical assessments of drug-likeness. 

The team’s findings, now published in the Journal of Medicinal Chemistry, suggests that MASH patients could be treated with cyclophilin-B targeted inhibitors, potentially offering new opportunities for those who do not respond to the only existing treatment.

This is the culmination of a decade of work that started with basic research in computational chemistry, opening up translational opportunities to benefit human health.

Prof. Julien Michel Study lead

Next steps

The team’s technology has been patent protected by Edinburgh Innovations and is now progressing towards in vivo and clinical studies. This publication represents a milestone that opens up opportunities for co-development, licensing, and collaborative ventures.

Read the paper in Journal of Medicinal Chemistry:

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