JR14a is a potent thiophene antagonist of human complement C3a receptor. JR14a shows selectivity for the human C3a receptor over C5a receptor. JR14a can suppress C3aR-mediated inflammation[1].
JR14a (0.1 nM-100 μM) inhibits C3a-induced intracellular Ca2+ release in human monocyte-derived macrophages, with an IC50 of 10 nM[1].JR14a (0.1 nM-100 μM) is metabolically stable to exposure over 1 h to rat liver microsomes[1].JR14a (0.1 nM-100 μM) inhibits C3a-induced β-hexosaminidase secretion in human LAD2 mast cells, with an IC50 of 8 nM[1].
JR14a (10 mg/kg; p.o. 2 h prior) reduces paw swelling by 65% over control at 30 min after agonist injection in acute rat paw model of inflammation and edema[1].JR14a (1 mg/kg; i.v.) exhibits elimination half-life (191 min), clearance (4.4 mL/min/kg) and AUC (3795 ng•h/mL) in rats[1].JR14a (10 mg/kg; p.o.) exhibits Cmax (88 ng/mL), Tmax (300 min) and AUC (478 ng•h/mL) in rats[1].
[1]. Rowley JA, et, al. Potent Thiophene Antagonists of Human Complement C3a Receptor with Anti-Inflammatory Activity. J Med Chem. 2020 Jan 23;63(2):529-541.