The goal of the project is the discovery of ligands of the receptor TGR5 as pharmacological tools and potential therapeutic agents for the treatment of diseases linked to cholesterol and bile acid metabolism and homeostasis.
This project is a multidisciplinary project in collaboration with the teams of Bart Staels (U1011), Jürgen Siepmann (U1008) and Philippe Chavatte (EA4481) which integrates all the aspects of drug discovery (screening, molecular modeling, cell and animal biology, pharmacokinetic and industrial property). A library of 20.000 compounds has been screened on the receptor and allowed the identification of hits from diverse chemical series. 5 chemicals series have been selected for further optimization. The conception of analogs will be assisted by molecular modelling. A pharmacophoric model is being validated and will allow the in silico screening of compound generated in the lab by the software Pipeline PilotTM.
Three TGR5 agonists of the literature have been synthesized and allow the calibration of the secondary assays and in vivo tests by the biologists of the project. More than 50 analogs have been synthesized and tested on both murine and human TGR5 receptor. First results allowed to understand the structure-activity relationships. We are now working in parallel on 3 chemicals series.
2018
2016
2015
2019
2017
2016
2015
Prizes and Awards
2017
2018
2017