Targeting proteinase-activated receptors: Therapeutic potential and challenges

Authors

Rithwik Ramachandran, University of Calgary
Farshid Noorbakhsh, University of Calgary
Kathryn Defea, University of California, Riverside
Morley D. Hollenberg, University of Calgary

Document Type

Article

Publication Date

1-1-2012

Journal

Nature Reviews Drug Discovery

Volume

11

Issue

1

First Page

69

Last Page

86

URL with Digital Object Identifier

10.1038/nrd3615

Abstract

Proteinase-activated receptors (PARs), a family of four seven-transmembrane G protein-coupled receptors, act as targets for signalling by various proteolytic enzymes. PARs are characterized by a unique activation mechanism involving the proteolytic unmasking of a tethered ligand that stimulates the receptor. Given the emerging roles of these receptors in cancer as well as in disorders of the cardiovascular, musculoskeletal, gastrointestinal, respiratory and central nervous system, PARs have become attractive targets for the development of novel therapeutics. In this Review we summarize the mechanisms by which PARs modulate cell function and the roles they can have in physiology and diseases. Furthermore, we provide an overview of possible strategies for developing PAR antagonists. © 2012 Macmillan Publishers Limited. All rights reserved.