JNJ-55308942

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

JNJ-55308942 是一种新型高效 P2X7 拮抗剂，对大鼠和人 hP2X7 的 Ki 分别为 1.0 和 6.5 nM，对一组相关 P2X 受体（P2X1、P2X2、P2X3、P2X2/3 和 P2X4）表现出显着活性；也表现出不显着的活性。抑制九种 CYP 异构体 (IC50>15 uM)。

JNJ-55308942 is a novel highly potent P2X7 antagonist with Ki of 1.0 and 6.5 nM for rat and human hP2X7, demonstrates significant activity against a panel of related P2X receptors (P2X1, P2X2, P2X3, P2X2/3, and P2X4; also shows insignificant inhibition of nine CYP isoforms (IC50>15 uM); exhibits excellent P2X7 receptor occupancy in the hippocampus of rats with low ED50 of 0.07 mg/kg and unbound plasma EC50 of 12 ng/mL, suppresses brain IL-1β release in vivo in freely moving rats challenged with the P2X7 agonist Bz-ATP; possesses good tolerability margins in preclinical species, as well as an acceptable cardiovascular safety profile in vivo.Epilepsy Phase 1 Clinical.

——

Animal Model:Sixteen male C57/BL6J mice Dosage: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, Vss, CL, Cmax and AUC24h were 81%, 1.7 L/kg, 3.7 mL min/kg, 1747 ng/mL, and 17549 (ng/mL) h, respectively.

JNJ55308942

Membrane Transporter/Ion Channel

P2X Receptor

P2X Receptor

Neurological Disease

Epilepsy

2166558-11-6

425.323

C17H12F5N7O

>98% (HPLC)

In Vitro:?DMSO : 100 mg/mL (235.12 mM)

——

(S)-(3-fluoro-2-(trifluoromethyl)pyridin-4-yl)(1-(5-fluoropyrimidin-2-yl)-6-methyl-1,4,6,7-tetrahydro-5H-[1,2,3]triazolo[4,5-c]pyridin-5-yl)methanone

(-20℃)

With Ice Pack

≥ 2 years