Production of next generation modulators of pannexins and connexins as novel therapeutics in the treatment of inflammatory cardiovascular and hepatic diseases

The modulation of membrane-bound proteins by drugs is receiving increasing attention from both academia and industry. Among such proteins are pannexin1 (Panx1), connexin43 (Cx43) and connexin32 (Cx32) that form hemichannels at the plasma membrane surface. These hemichannels mediate cellular communication and have emerged as key players in inflammation. This carries translational relevance, as hemichannel inhibition could represent an innovative strategy for the treatment of a plethora of diseases. However, a hurdle in clinical exploration is the lack of appropriate hemichannel inhibitors. PANACHE therefore is a timely project, as it will generate a new type of Panx1, Cx43 and Cx32 hemichannel inhibitors. As proof-of-concept, the generated Panx1, Cx43 and Cx32 hemichannel inhibitors will be tested for their potential to alleviate pathological features in animal models of inflammatory diseases in the cardiovascular system, liver and joints. This will be accomplished by joining academic and industrial scientists from the chemical, chemo-informatics and biomedical fields as well as by relying on in vitro and in silico studies, animal experimentation and testing human material. PANACHE will allow taking a leap forward to the realization of its long-term vision, namely the production of metabolically robust and selective Panx1, Cx43 and Cx32 hemichannel inhibitors that can be used for the establishment of a generic approach to synergize current therapy of hard-to-treat inflammatory diseases. Hence, PANACHE is a foundational project, laying the basis for follow-up initiatives to scrutinize the versatile anti-inflammatory therapeutic actions of the Panx1, Cx43 and Cx32 hemichannel inhibitors

This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No […]