CE-224535

CE-224535 is a selective P2X₇ receptor antagonist. IC50 & Target: P2X₇ receptor^[1] In Vitro: CE-224535 is developed as a disease-modifying antirheumatic drugs (DMARD) and is a selective antagonist of the human P2X₇ receptor. CE-224535 can reduce leukocyte secretion of IL-1 and IL-18, thereby providing a novel therapeutic approach for treatment of rheumatoid arthritis (RA)^[1]. In Vivo: In rats, CE-224535 has low CL_p (11 mL/min/kg) and a large V_dss of 7.6 L/kg, which results in a half-life of 2.4 h. Upon oral administration to rats at 5 mg/kg, CE-224535 provides maximal plasma exposure (C_max) that is ~90 fold over its IC₉₀ in human blood (C_max=0.21 μg/mL or 0.44 μM). The oral bioavailability of CE-224535 is low in rats (F=2.6%), but this is believed to be a rat specific phenomenon since corresponding oral bioavailability in both dog (59%) and monkey (22%) is adequate^[2].