Robert K. Y. Cheng; Cédric Fiez-Vandal; Oliver Schlenker; Karl Edman; Birte Aggeler; Dean G. Brown; Giles A. Brown; Robert M. Cooke; Christoph E. Dumelin; Andrew S. Doré; Stefan Geschwindner; Christoph Grebner; Nils-Olov Hermansson; Ali Jazayeri; Patrik Johansson; Louis Leong; Rudi Prihandoko; Mathieu Rappas; Holly Soutter; Arjan Snijder; Linda Sundström; Benjamin Tehan; Peter Thornton; Dawn Troast; Giselle Wiggin; Andrei Zhukov; Fiona H. Marshall; Niek Dekker
Nature, 2017, 545, 112-115
https://doi.org/10.1038/nature22309

Abstract

Protease-activated receptors (PARs) are a family of G-protein-coupled receptors (GPCRs) that are irreversibly activated by proteolytic cleavage of the N terminus, which unmasks a tethered peptide ligand that binds and activates the transmembrane receptor domain, eliciting a cellular cascade in response to inflammatory signals and other stimuli. PARs are implicated in a wide range of diseases, such as cancer and inflammation1, 2, 3. PARs have been the subject of major pharmaceutical research efforts3 but the discovery of small-molecule antagonists that effectively bind them has proved challenging