A refined agonist pharmacophore for protease activated receptor 2

Protease activated receptor 2 (PAR2) is a G protein-coupled receptor implicated in inflammation and cancer. Only a few peptide agonists are known with greater potency than the native agonist SLIGRL-NH2. Here we report 52 peptide agonists of PAR2, 26 with activity at sub-micromolar concentrations, and one being iodinated for radioligand experiments. Potency was highest when the N- or C-termini of SLIGRL-NH2 were modified, pointing to a new ligand pharmacophore model that may aid development of drug-like PAR2 modulators.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide