JNJ-47965567 是中枢通透性、高亲和力、选择性的P2X7拮抗剂，可用于探讨中枢 P2X7 在中枢神经系统病理生理模型中的作用。它对人和大鼠 P2X7 作用的pKi值分别为 7.9 和 8.7。

JNJ-47965567 is a selective antagonist of the purinergic receptor P2X subtype 7 (P2X7), a ligand-gated ion channel(with pKis of 7.9 and 8.7 for human and rat P2X7, respectively).

JNJ-47965567 is potent high affinity (pKi 7.9 0.07), selective human P2X7 antagonist, with no significant observed speciation.?In native systems, the potency of the compound to attenuate IL-1β release was 6.7 0.07 (human blood), 7.5 0.07 (human monocytes) and 7.1 0.1 (rat microglia).?JNJ-47965567 exhibited target engagement in rat brain, with a brain EC50 of 78 19 ng·mL(-1) (P2X7 receptor autoradiography) and functional block of Bz-ATP induced IL-1β release.?JNJ-47965567 (30 mg·kg(-1) ) attenuated amphetamine-induced hyperactivity and exhibited modest, yet significant efficacy in the rat model of neuropathic pain.?No efficacy was observed in forced swim test.

The authors used a combination of in vitro assays (calcium flux, radioligand binding, electrophysiology, IL-1β release) in both recombinant and native systems.?Target engagement of JNJ-47965567 was demonstrated by ex vivo receptor binding autoradiography and in vivo blockade of Bz-ATP induced IL-1β release in the rat brain.?Finally, the efficacy of JNJ-47965567 was tested in standard models of depression, mania and neuropathic pain

1428327-31-4

C28H32N4O2S

488.65

JNJ-479655

DMSO:200 mg/mL (409.30 mM),Need ultrasonic
Powder: -20°C for 3 years
In solvent: -80°C for 2 years