Background:

AC 264613 is a potent agonist of PAR2 with pEC50 value of 7.5 and potencies range from 30 to 100 nM [1, 2].

Protease-activated receptor 2 (PAR2) also known as coagulation factor II (thrombin) receptor-like 1 (F2RL1) or G-protein coupled receptor 11 (GPR11) is expressed in vascular tissue and highly vascular organs and involves in the vascular tone regulation. It has been shown that PAR2 plays a pivotal role in vessel inflammation and wound healing processes [2].

AC 264613 is a selective PAR2 agonist and has no effect on other PARs. When tested with HEK 293 T cells (PAR2 wild type) and KNRK cells (transfected with human PAR2 receptors) for stimulates PI hydrolysis and Ca2+ mobilization assays, AC 264613 showed effect with pEC50 value of 6.9 and 7.0,respectively [1]. Using QuickChange Mutagenesis manner, NIH 3T3 cells were made with ECL2 mutations in Q233E, E232R, E232R/Q233R, F240S, and F240S/S37P receptors and AC 264613 treatment PAR2 F240S receptors were constitutively expressed in multiple functional endpoints while had no effect on E232 and Q233 mutaions [2].

In male Sprague-Dawley rat model with acute thermal nociception and edema in paw induced by SLIGRL-NH2 or trypsin, intrapaw administration of AC 264613 induced hind paw edema and thermal hyperalgesia at the doses as low as 30 ng and showed dose-dependent pronociceptive effects [1].

参考文献:
[1].  Gardell, L.R., et al., Identification and characterization of novel small-molecule protease-activated receptor 2 agonists. J Pharmacol Exp Ther, 2008. 327(3): p. 799-808.
[2].   Ma, J.N. and E.S. Burstein, The protease activated receptor 2 (PAR2) polymorphic variant F240S constitutively activates PAR2 receptors and potentiates responses to small-molecule PAR2 agonists. J Pharmacol Exp Ther, 2013. 347(3): p. 697-704.