BioAscent is delighted to announce the recent publication of its successful collaboration with the University of Edinburgh in the Journal of Medicinal Chemistry. This cutting-edge research, led by Professor Julien Michel, describes the development of novel cyclophilin B inhibitors for the treatment of metabolic dysfunction-associated steatohepatitis (MASH).

MASH is a progressive liver disease caused by inflammation that can lead to cirrhosis, liver failure and liver cancer. Treating this condition remains challenging, with obesity, type 2 diabetes and high levels of LDL cholesterol all recognised as risk factors for developing this disease. MASH affects an increasing number of people worldwide; it is estimated that around 250 million people are living with this chronic condition, with up to 6.5% of adults in the US estimated to have MASH.¹

Despite its prevalence, treatment options for MASH are limited, making it an area of significant unmet medical need. In 2024, thyroid hormone receptor-b agonist Resmetirom became the first FDA-approved therapy for MASH. While this represents a significant milestone, drawbacks such as limited clinical efficacy and high treatment costs highlight the ongoing need for new therapeutic options.

The team at the University of Edinburgh is working at the forefront of MASH drug discovery, exploring novel therapeutic pathways. One promising target is cyclophilin B, a protein implicated in liver fibrosis. Free energy perturbation modelling was used to design novel, potent cyclophilin B inhibitors. In cellular models, these compounds showed similar efficacy to Resmetirom, as well as isoform selectivity, and a promising pharmacokinetic profile in early in vitro DMPK studies, making them excellent candidates for further development. 

BioAscent’s chemists collaborated closely with the Edinburgh team to rapidly and efficiently develop and synthesise novel ligands for this project. Our scientists applied problem-solving skills and critical thinking to overcome key challenges throughout the project, exemplifying BioAscent’s collaborative approach – working in partnership with our clients to understand their goals and deliver tailored solutions.

Dr Angus Morrison, Director of Chemistry, says: “We were pleased to support the synthesis of the cyclophilin B-targeting compounds featured in this study. Contributing to a program focused on MASH, where therapeutic innovation is urgently needed, was a meaningful opportunity for our chemistry team. It was especially rewarding to collaborate with Julien Michel and his group to help advance these molecules toward biological evaluation.”

At BioAscent, we are proud to have contributed to advancing this research towards achieving in vivo proof of concept, and we look forward to following this exciting programme as it moves forward.

References: 1.         https://www.niddk.nih.gov/health-information/liver-disease/nafld-nash/definition-facts