BioCentury
ARTICLE | Translation in Brief

Heptares up to PAR2

Heptares solves PAR2 structure, partners with AZ for new anti-PAR2 pain compounds

February 12, 2015 8:00 AM UTC

Heptares Therapeutics Ltd. has solved the long sought-after X-ray structure of Protease-activated receptor (PAR2), a difficult-to-express GPCR that is activated by proteolytic cleavage. Now its partner AstraZeneca plc has used the structure to identify the first inhibitors of PAR2, and is lining them up to test in pain and inflammation.

PAR2 has been linked to neurogenic inflammation and pain - in particular bone pain in cancer, gastrointestinal pain and osteoarthritis - but has thus far eluded drug developers. The receptor differs from most GPCRs as it is activated by cleavage of its large extracellular domain, and the released peptide fragment acts as the natural ligand. That has made PAR2 particularly difficult to express in a stable form, largely because of the difficulty of finding high affinity ligands needed to lock it in a stable configuration...