AZ8838 is a potent, competitive, allosteric, orally active non-peptide small molecule antagonist of PAR2 with a pKi of 6.4 for hPAR2[1].
AZ8838 binds in an occluded pocket[1].AZ8838 is a potent antagonist against SLIGRL-NH2 in the Ca2+ assay with a pIC50 of 5.70 ± 0.02[1].AZ8838 shows a potency trend when inhibiting IP1 production (pIC50 = 5.84 ± 0.02)[1].AZ8838 attenuates both peptide-induced phosphorylation of ERK1/2 (pIC50 = 5.7 ± 0.1) and β-arrestin-2 recruitment (pIC50 = 6.1 ± 0.1)[1].
AZ8838 (10 mg/kg; p.o.; 2 h prior) is anti-inflammatory in a PAR2 agonist-induced rat paw oedema model[1].
[1]. Kennedy AJ, et al. Protease-activated receptor-2 ligands reveal orthosteric and allosteric mechanisms of receptor inhibition. Commun Biol. 2020 Dec 17;3(1):782.