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].
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: | Pharmacokinetic Parameters of JPE-1375 in C57BL/6J wild-type mice[1].
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[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.