Lundbeckfonden - Development of tool compounds for evaluation of the fatty acid receptor FFA3 as drug target

  • Rexen Ulven, Elisabeth (Head coordinator)

Project: Research

Project Details


A fiber-rich diet has beneficial health effects on metabolic, inflammatory and cardiovascular
diseases. Dietary fiber is fermented by the microbiota in the intestines to short-chain fatty
acids (SCFAs), which are believed to mediate health effects partly through the fatty acid
receptor FFA3. In 2003, FFA3 was reported to be activated by SCFAs and since then FFA3
has been considered a nutrient sensing receptor and suggested to be a target for treatment of inflammatory and metabolic disorders. FFA3 has been linked to secretion of the satiety
hormone PYY and the incretin GLP-1, and reported to protect against allergic inflammation
in lung. However, several contradictory findings have been reported and the physiological
functions of FFA3 are still unclear. Currently, selective and potent agonists and antagonists
required for critical studies on the receptor are lacking. This project aims at developing such
potent and selective tool compounds using two different main approaches based on either
fusing allosteric ligands with orthosteric small carboxylic acids or virtual screening of
databases to identify new scaffolds. Fluorescent tool compounds will be developed on basis
of the new ligands. These tools will enable studies that are critical to evaluate the
physiological functions and drug target potential of FFA3.
Effective start/end date01/09/201531/10/2018