AC 55541 CAS NO.916170-19-9

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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 agonist Neither 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.