Lu AF27139

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

Lu AF27139 是一种有效的选择性 P2X7 受体拮抗剂（人和大鼠的 IC50 分别为 12 和 2.4 nM，小鼠、人和大鼠的 Ki 分别为 22、54 和 13 nM）。 Lu AF27139可用于中枢神经系统疾病研究。

Lu AF27139 is an effective and selective antagonist of P2X7 receptor (IC50s of 12 and 2.4 nM for human and rat, Kis of 22, 54, and 13 nM for mouse, human, and rat, respectively). Lu AF27139 can be used in CNS diseases studies.(In Vitro):Lu AF27139 (100 nM) inhibits 300 μM BzATPinduced current in primary rat microglia with 80% inhibition occurring at a 100 nM dose.Lu AF27139 inhibits LPS-primed and BzATP-induced IL-1β release from THP-1 cells with an IC50 of 38 ± 2.5 nM. Lu AF27139 concentration-dependently blocks IL-1β release in rat and mouse primary cortical microglia primed with LPS and induces with 1 mM BzATP with IC50’s of 38 ± 19 nM in rat and 26 ± 6 nM in mice. Lu AF27139 (10-200 nM) inhibits 100 μM BzATP-induced current in HEK293 cells stably transfected with the rat P2X7R in a dose response manner with an IC50 of 66 nM.(In Vivo):In male Sprague?Dawley rats and male C57BL mice, Lu AF27139 (p.o.; 3, 10, and 100 mg/kg) reduces intracerebroventricular administered LPS-primed and BzATP-triggered IL-1β release in the frontal cortex.

Lu AF27139 (compound 1) (10-200 nM) inhibits 100 μM BzATP-induced current in HEK293 cells stably transfected with the rat P2X7R in a dose response manner with an IC50 of 66 nM.Lu AF27139 (compound 1) (100 nM) inhibits 300 μM BzATPinduced current in primary rat microglia with 80% inhibition occurring at a 100 nM dose.Lu AF27139 (compound 1) inhibits LPS-primed and BzATP-induced IL-1β release from THP-1 cells with an IC50 of 38 ± 2.5 nM.Lu AF27139 (compound 1) concentration-dependently blocks IL-1β release in rat and mouse primary cortical microglia primed with LPS and induces with 1 mM BzATP with IC50’s of 38 ± 19 nM in rat and 26 ± 6 nM in mice.

Lu AF27139 (compound 1) (p.o.; 3, 10, and 100 mg/kg) reduces intracerebroventricular (icv) administered LPS-primed and BzATP-triggered IL-1β release in the frontal cortex of rats and mice.Assessment of Pharmacokinetics (PK) profile of Lu AF27139 (compound 1) in rat. Free plasma, brain, and spinal cord concentrations of Lu AF27139 in rat were determined by the formula (Ct*fu), where Ct is the total tissue (plasma, brain, or spinal cord) drug concentration and fu is the fraction unbound in these tissues as determined by ex vivo equilibrium dialysis. Values are expressed as mean ± SEM for n = 3 animals. fu, plasma = 0.02 ± 0.00, fu, spinal cord = 0.07 ± 0.03, and fu, brain = 0.09 ± 0.03. Values are expressed as mean ± SEM for n ≥ 3 experiments. Animal Model:Male Sprague?Dawley rats (280?350 g); Male C57BL mice (18?25g).Dosage:3, 10, and 100 mg/kg Administration:p.o.Result:Reduced intracerebroventricular (icv) administered LPS-primed and BzATP-triggered IL-1β release in the frontal cortex of rats and mice.

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Membrane Transporter/Ion Channel

P2X Receptor

DHODH

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2097117-06-9

497.92

C21H19ClF3N5O2S

>98% (HPLC)

In Vitro:?DMSO : 125 mg/mL (251.04 mM)

O=C(c1c(C(F)(F)F)nc(-c2ncccn2)s1)NC[C@H](c(cc1)ccc1Cl)N1CCOCC1

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(-20℃)

With Ice Pack

≥ 2 years