Biological Activity
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].
References
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.
