Collaboration breeds success: Discovery of a new chemical class to investigate role of EPAC proteins in diabetes and cardiovascular diseases

24 January 2020

Scientists from the Yarwood Lab and the European Screening Centre have jointly published on the discovery of a new class of EPAC activators. The study, which describes the identification, optimisation and characterisation of a new chemical class of selective agonists for EPAC1, is the result of another successful collaboration within the framework of the European Lead Factory (ELF).

Image: Example pose of cyclic AMP analogue, D-007 (left), and SY000 (right) bound to an EPAC1 homology model (based on PDB 4HMO).

After a full deck high-throughput screen of the ELF Compound Library, several orthogonal assays were performed to select the most relevant hits. Subsequently, and guided by in-silico modelling, the team synthesized analogues of these hits with enhanced properties. Further characterisation in in vitro and in cellulae EPAC1 activation assays demonstrated the selectivity and cellular activity of the molecules.  

The compounds resulting from this study represent powerful experimental tools for the investigation of EPAC1 function in the development of future therapeutic strategies for multiple disorders, including type 2 diabetes and cardiovascular diseases.

Read the abstract and download the full PDF here.