Skip to main content
European Commission logo print header

Targeting NLRP3-mediated inflammation with novel chemotypes

Project description

Targeted anti-inflammatory therapeutics

Inflammation is a natural defence mechanism against pathogens, trauma or damage that involves various receptors and sensors, collectively known as inflammasome. Sensing receptors in the membrane or cytosol of specific immune and other cells can recognise pathogen-associated or damage-associated molecular patterns. NLRP3 is such a receptor, known to be implicated in various chronic inflammatory diseases. Funded by the European Research Council, the PyroScreen project aims to identify novel NLRP3 inhibitors and analyse their mode of action, selectivity and efficacy. Results will contribute towards the development of NLRP3 therapeutics against inflammatory diseases.

Objective

Inflammasomes play a vital role in in protecting humans against pathogenic microorganisms, harmful substances and cell changes that could result in illness. The NLRP3 inflammasome in particular attracts considerable interest because aberrant NLRP3 activation is a key pathogenic mechanism in many chronic inflammatory diseases. Moreover, gain-of-function mutations in NLRP3 causes a periodic fever syndrome named cryopyrin-associated periodic syndrome (CAPS). MCC950/CRID3-based sulfonylurea compounds are currently the only reported class of inhibitors that selectively target NLRP3 with nM potency. We and others recently showed that members of this sulfonylurea class inhibitors directly target the central NACHT domain of NLRP3, and several companies have recently progressed MCC950/CRID3-derived NLRP3 inhibitors to human studies. However, there is an urgent need to expand the pipeline of NLRP3-targeted therapeutics with NLRP3-inhibitors of novel chemotypes. Based on exciting preliminary data, we aim to identify novel NLRP3 inflammasome inhibitors and perform an in-depth functional analysis of their activity, selectivity and molecular mechanism of action. Furthermore, we will define the market potential and explore the best strategy towards clinical development with partner organizations. In conclusion, the project will help to expand the pipeline of NLRP3-targeted therapeutics with new NLRP3-inhibitors. If successful, the project may meaningfully impact on the lives of many patients that suffer from NLRP3-mediated diseases in Europe and across the globe.

Keywords

æ

Coordinator

UNIVERSITEIT GENT
Net EU contribution
€ 150 000,00
Address
Sint pietersnieuwstraat 25
9000 Gent
Belgium

See on map

Region
Vlaams Gewest Prov. Oost-Vlaanderen Arr. Gent
Activity type
Higher or Secondary Education Establishments
Links
EU contribution
No data