Novel molecular agents for the treatment of MASH

Application

Small molecule treatment for MASH

Development Status

Ongoing development

IP Status

• PCT/EP2019/073106
• US granted 2023​
• EU under examination

Commercial Offerings

Licensing or collaborative research

Opportunity

Metabolic dysfunction-associated steatohepatitis (MASH, previously NASH) is the most common chronic liver condition, with a prevalence of 30%, and the leading cause of liver transplants. The MASH pathophysiology is thought to be significantly driven by cyclophilins, and their inhibition is emerging as a key therapeutic strategy for attenuating liver fibrosis in MASH patients. However, current trialled cyclophilin inhibitors lack subtype selectivity and have not arrived on the market for MASH treatment. University of Edinburgh inventors have developed a novel class of cyclophilin inhibitors that shows subtype cyclophilin selectivity and improved in vitro activity on human liver model cells of MASH.

Technology

Scientists at the University of Edinburgh have developed a new library of cyclophilin inhibitors with strong potential for the treatment of MASH by selectively inhibiting cyclophilin B, a key target for attenuating MASH-related fibrosis. Unlike most of the current cyclophilin inhibitors under clinical trials, this new class of inhibitors show target and cell type selectivity, are not genotoxic, and present improved pharmaceutical properties. In vitro studies on the lead compound offer promising results for the further development of the new generation of MASH treatments.

Benefits

• Small molecules to develop new treatments of cyclophilin-driven fibrosis-associated conditions including those in the liver such as MASH.
• In vitro validated compounds showing promising uses for MASH treatment.
• Library of cyclophilin inhibitors showing tuneable target selectivity, simple synthesis route, reduced toxicity and improved DMPK properties.

Publication

‘Optimization of Cyclophilin B-Targeted Tri-vector Inhibitors for Novel MASH Treatments’

Maria-Eleni Kouridaki, Jonathan Gillespie, John Robinson, Tanya Mathie, Laura Bain, Duncan McArthur, Angus Morrison, Daniel B. Greenslade, Michail Papadourakis, Kasia Maj, Kate Cameron, Darryl Turner, Scott P. Webster, Martin A. Wear, Dahlia Doughty-Shenton. Alison N. Hulme, Julien Michel.

J. Med. Chem., ASAP, 2025 doi:10.1021/acs.jmedchem.5c00301

Quote: TEC1104125