The goal of the ERC Proof of Concept CYPNASH activity was to develop further a novel class of ‘trivector’ cyclophilin inhibitors that were discovered during the activities of the previously funded ERC Starting Grant EBDD. Such molecules may possess advantages over existing classes of cyclophilin inhibitors to enable new medical treatments for non-alcoholic steatohepatitis, a prevalent liver disease. During the lifetime of the project two libraries of trivector derivatives were designed, synthesised and tested in biological assays. The project has led to the identification of a lead series that possesses superior drug-like properties to first generation trivector inhibitors and may be progressed towards late stage preclinical studies. The results of this project will facilitate the development of future medicines based on pharmacological inhibition of cyclophilins.
