JPE-1375

JPE-1375 is a complement C5a receptor 1 (C5aR1) antagonist. JPE-1375 effectively inhibits polymorphonuclear leukocyte mobilization (EC50=6.9 µM) and reduces TNF levels (EC50=4.5 µM) in mice. JPE-1375 can be used in studies of autoimmune and inflammatory diseases[1].

Signaling Pathways >> Immunology/Inflammation >> Complement System

Research Areas >> Inflammation/Immunology

C5aR1[1].

JPE-1375 (0.3, 1.0, 3.0 mg/kg; i.v.; single) inhibits PMN (polymorphonuclear leukocytes) mobilization and TNF with EC50 values of 6.9 and 4.5 µM, respectively[1]. JPE-1375 (1 mg/kg; i.v.; single) demonstrates a rapid distribution in the plasma, followed by elimination in mice[1]. JPE-1375 (1 mg/kg; i.v.; single) shows a strong negative correlation between PMN mobilization and TNF production with plasma concentrations[1]. Animal Model: C57BL/6J wild-type (10 to 12-week-old; C5a pharmacodynamic model)[1]. Dosage: 0.3, 1.0, 3.0 mg/kg Administration: Intravenous injection; single. Result: Significantly decreased C5a-mediated PMN mobilization at 1 and 3 mg/kg doses, while no effect was observed at a 0.3 mg/kg dose. Showed a significant reduction in TNF plasma levels at 1 and 3 mg/kg dose with both compounds reducing C5a-mediated TNF by about 90%. Animal Model: C57BL/6J wild-type mice(10 to 12-week-old)[1]. Dosage: 1 mg/kg Administration: Intravenous injection; single. Result: 1.19Pharmacokinetic Parameters of JPE-1375 in C57BL/6J wild-type mice[1]. IV (1 mg/kg) T1/2 (h) 0.13 Cmax (µg/mL) 7.18 AUC0-t (μg/mL•h) 2.40 AUC0-inf, obs (μg/mL•h) 2.41 AUC0-t/0-inf, obs (μg/mL•h) 1.00 AUMC0-inf, obs (μg/mL•h2) 0.13 MRT0-inf, obs (h) 0.05 Vz, obs ((μg)/(μg/mL)) 2.38 CL, obs ((μg)/(μg/mL)/h) 12.47 Vss, obs ((μg)/(μg/mL)) 0.66

[1]. Cui CS, et al. In Vivo Pharmacodynamic Method to Assess Complement C5a Receptor Antagonist Efficacy. ACS Pharmacol Transl Sci. 2021 Dec 21;5(1):41-51.