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

Project description

Hemichannel inhibitors used in novel treatment of inflammatory diseases

Cell membrane proteins pannexin1, connexin43 and connexin32 form hemichannels at the plasma membrane surface; these hemichannels have emerged as a key players in cellular communication and inflammation. The hemichannel inhibition could represent an innovative strategy for inflammation treatment, but there is a lack of appropriate hemichannel inhibitors. The goal of the EU-funded PANACHE project is to generate a novel type of hemichannel inhibitor. As proof of concept, the new generation of hemichannel inhibitors will be tested for their potential to alleviate inflammatory diseases in the cardiovascular system, liver and joints, using animal models. PANACHE is a foundational project, linking efforts of academic and industrial scientists for the realisation of a long-term strategy of hemichannel inhibitor production with potential for use in establishing a complex therapy of hard-to-treat inflammatory diseases.

Objective

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 and liver. 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.

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Programme(s)

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Topic(s)

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Funding Scheme

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RIA - Research and Innovation action

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Call for proposal

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(opens in new window) H2020-FETOPEN-2018-2020

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Coordinator

VRIJE UNIVERSITEIT BRUSSEL
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 793 167,44
Address
PLEINLAAN 2
1050 BRUSSEL
Belgium

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Region
Région de Bruxelles-Capitale/Brussels Hoofdstedelijk Gewest Région de Bruxelles-Capitale/ Brussels Hoofdstedelijk Gewest Arr. de Bruxelles-Capitale/Arr. Brussel-Hoofdstad
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 793 167,44

Participants (3)

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