JNJ-55308942

小分子

JNJ-55308942

J655878-1ml

1ml

10mM in DMSO

避光,干燥,-80℃储存

超低温冰袋运输

JNJ-55308942 is a high-affinity, selective, brain-penetrant P2X7 functional antagonist (hP2X7: IC 50 =10 nM, K i =7.1 nM; rP2X7: IC 50 =15 nM, K i =2.9 nM). JNJ-55308942 is orally bioavailable, binds to brain P2X7 and blocks IL-1β release from adult rodent brain. In Vitro JNJ-55308942 shows pK i s of 8.1and 8.5 for recombinant human and rat P2X7 channels, respectively. In human blood and in mouse blood and microglia, JNJ-55308942 attenuates IL-1β release in a potent and concentration-dependent manner. MCE has not independently confirmed the accuracy of these methods. They are for reference only. In Vivo JNJ-55308942 (30 mg/kg; p.o.) attenuates LPS-induced microglial activation in mice. In a model of Bacillus Calmette-Guerin (BCG)-induced depression, JNJ-55308942 dosed orally (30 mg/kg), reversed the BCG-induced deficits of sucrose preference and social interaction. After oral dosing, the compound exhibited both dose and concentration-dependent occupancy of rat brain P2X7 with an ED 50 of 0.07 mg/kg. The P2X7 antagonist (3 mg/kg, oral) blocked Bz-ATP-induced brain IL-1β release in conscious rats, demonstrating functional effects of target engagement in the brain. JNJ-55308942 (5 mg/kg; p.o.) shows the F, V ss , CL, C max and AUC 24h values are 81%, 1.7 L/kg, 3.7 mL min/kg, 1747 ng/mL, and 17549 (ng/mL) h, respectively . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Sixteen male C57/BL6J miceDosage: 30 mg/kg Administration: P.o. (after an i.p. injection of LPS (0.8 mg/kg, i.p.)) Result: Significantly attenuated the effect of LPS on FSC, CD45 surface expression and CD11b surface expression. Animal Model: Rat Dosage: P.o. (Pharmacokinetic Analysis) Administration: 5 mg/kg Result: The F, V ss , CL, C max and AUC 24h were 81%, 1.7 L/kg, 3.7 mL min/kg, 1747 ng/mL, and 17549 (ng/mL) h, respectively.

JNJ-55308942 是一种高亲和性、选择性、脑穿透性 P2X7 功能拮抗剂（hP2X7：IC 50 =10 nM，K i =7.1 nM；rP2X7：IC 50 =15 nM，K i =2.9 nM）。JNJ-55308942 具有口服生物可利用性，能与脑 P2X7 结合，并能阻断成鼠 IL-1β 的释放。

2166558-11-6(DMSO)

C17H12F5N7O

425.32 g/mol

CC1CC2=C(CN1C(=O)C3=C(C(=NC=C3)C(F)(F)F)F)N=NN2C4=NC=C(C=N4)F