Discover chemical modulators of the ERAP 1 and/or 2 enzymes involved in antigen presentation
Many antigenic peptides presented by MHC class I molecules are initially created through proteolysis by the proteasome as precursors. The trimming of these precursors to the final epitope is performed in the ER by ERAP-1 and ERAP-2. Genome wide Association Studies have linked ERAP1 and ERAP2 with predisposition to human diseases with autoimmune aetiology such as rheumatic diseases (most notably Ankylosing Spondylitis), and type I diabetes as well as with bacterial and viral. Also, Pr Stratikos team in Athens has contributed significantly to the understanding of the function of these proteases and has published their 3D-structure. The available evidences for a significant impact of ERAP1/2 on human health suggest that pharmacological modulation of ERAP function may be of medical interest. So far, apart from non selective compounds such as amastin and leucinthiol, no selective and potent inhibitors of these enzymes are available.
While the short term goal of this proposal will be the identification of promising leads, the long term goal will be the generation of novel pharmacological approaches towards the treatment of ERAP-associated human diseases based on the modulation of antigen processing and adaptive immune responses.
The project “ERAPIMM” has been granted by ANR for 3 years (Nov 2020- Nov 2023).
The teams of
collaborate in a project aiming at discovering and developing of ERAP inhibitors as a new approach to treat autoimmune & auto-inflammatory diseases.
In particular, the teams will specifically study applications in Type 1 diabetes, Behcet’s disease and Spondyloarthritis.
Deprez-Poulain, R. Pharmacological modulation of antigen processing and presentation: new therapeutic approach for cancer and autoimmune diseases,4th Scientific Meeting of the Institut Pasteur de Lille,Marcq en Baroeul, France,18 Jun. 2018 Invited
Deprez-Poulain, R. Nouveaux médicaments du cancer et des maladies auto-immunes : dompter le système immunitaire à des fins thérapeutiques,Conférences 5à7 Médicaments,Institut Pasteur de Lille, France,17th Apr. 2018