AC-55541

AC-55541 is a novel small-molecule protease-activated receptor 2(PAR2) agonist; activated PAR2 signaling in cellular proliferation assays, phosphatidylinositol hydrolysis assays, and Ca(2+) mobilization assays, with potencies ranging from 200 to 1000 nM.IC50 value: 200-1000 nM(EC50) [1]Target: PAR2 agonistNeither AC-55541 nor AC-264613 had activity at any of the other PAR receptor subtypes, nor did they have any significant affinity for over 30 other molecular targets involved in nociception. Visualization of EYFP-tagged PAR2 receptors showed that each compound stimulated internalization of PAR2 receptors. AC-55541 was well absorbed when administered intraperitoneally to rats, reaching micromolar peak plasma concentrations. AC-55541 was stable to metabolism by liver microsomes and maintained sustained exposure in rats, with elimination half-lives of 6.1 h. Intrapaw administration of AC-55541 or AC-264613 elicited robust and persistent thermal hyperalgesia and edema. Coadministration of either a tachykinin 1 (neurokinin 1) receptor antagonist or a transient receptor potential vanilloid (TRPV) 1 antagonist completely blocked these effects. Systemic administration of either AC-55541 or AC-264613 produced a similar degree of hyperalgesia as was observed when the compounds were administered locally.

Signaling Pathways >> GPCR/G Protein >> Protease-Activated Receptor (PAR)

Research Areas >> Others

[1]. Gardell LR, et al. Identification and characterization of novel small-molecule protease-activated receptor 2 agonists. J Pharmacol Exp Ther. 2008 Dec;327(3):799-808.

TRAP-6 | AZ 3451 | SLIGKV-NH2 | PAR-4 (1-6) amide (mouse) trifluoroacetate salt | TFLLR-NH2 TFA | BMS-986120 | (Ala1)-PAR-4 (1-6) amide (mouse) trifluoroacetate salt | SLIGRL-NH2 2TFA | TRAP-5 trifluoroacetate salt