Background:

AC 55541 is a potent agonist of PAR2 with pEC50 value of 6.7 and functions range from 200 to 1000 nM [1-3].

Protease-activated receptor 2 (PAR2) is a member of the large family of 7-transmembrane receptors and plays an important role in modulating inflammatory responses and acting as a sensor for proteolytic enzymes generated during infection [2].

AC 55541 is a selective PAR2 agonist and has no effect on PAR1. Using a cellular proliferation assay (R-SAT), it showed that AC 55541 stimulated NIH-3T3 cells proliferation by activating PAR2 and receptor with F240S mutation constitutively active in all functional assays which nearly 30-fold sensitive to AC 55541 than SLIGRL and 2-furorl LIGRLO [1, 2]. When tested with human corneal epithelial (HCE) cells, administration of AC 55541 significantly induced the expression of PAR2 and inhibited Acanthamoeba plasminogen activator (aPA) [3].

In male Sprague-Dawley rat model with acute thermal nociception and edema in paw induced by SLIGRL-NH2 or trypsin, intrapaw administration of AC 55541 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.
3.   Tripathi, T., M. Abdi, and H. Alizadeh, Protease-activated receptor 2 (PAR2) is upregulated by Acanthamoeba plasminogen activator (aPA) and induces proinflammatory cytokine in human corneal epithelial cells. Invest Ophthalmol Vis Sci, 2014. 55(6): p. 3912-21.