PAR-1 agonist/ TRAP6 – GPCR Modulators

Protease activated receptors (PARs) are a distinctive four-member family of seven transmembrane G protein-coupled receptors (GPCRs) widely expressed in inflammatory cells. PARs are cleaved by certain serine proteases to expose a tethered ligand domain, this ligand domain then binds to and activates the receptors to initiate multiple signalling cascades. These PAR-activating proteases therefore represent PAR agonists. This PAR-1 agonist peptide represents the sequence of the ‘tethered ligand’ and is therefore capable of activating the receptor independently of N-terminal proteolysis. TFLLR-NH2 is more selective to PAR-1 than the PAR-1 agonist SFLLRN-NH2. Activation of PAR-1 induces platelet aggregation and IL-6 release from monocytes and T cells, as well as several other cellular pathways including those involved in allergic inflammation, neurogenic inflammation and the potentiation of NMDA receptor activity in the hippocampus.