Lu AF27139 是一种有效的、选择性的、具有口服活性的 P2X7 受体拮抗剂（IC50s 值对人和大鼠分别为 12 和 2.4 nM，Kis 对小鼠、人和大鼠分别为 22、54 和 13 nM ）。Lu AF27139 具有啮齿动物活性和 CNS 渗透特性。Lu AF27139 具有研究中枢神经系统疾病的潜力。
货号:ajcx36768
CAS:2097117-06-9
分子式:C21H19ClF3N5O2S
分子量：497.92
溶解度:DMSO : 125 mg/mL (251.04 mM; Need ultrasonic)
纯度：98%
存储：Store at -20°C
库存：现货

Background:

Lu AF27139 is a potent, selective, and orally active 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 has rodent-active and CNS-penetrant character. Lu AF27139 has the potential for the research of CNS diseases[1].

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[1].Lu AF27139 (compound 1) (100 nM) inhibits 300 μM BzATPinduced current in primary rat microglia with 80% inhibition occurring at a 100 nM dose[1].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[1].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[1].

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[1].Assessment of Pharmacokinetics (PK) profile of Lu AF27139 (compound 1) in rat[1]. dose Cu, plasma (nM)a Cu, brain (nM)aCu, spinal cord (nM)a (mg/kg, po) (1 h) (2 h) (1 h)(2 h)(1 h)(2 h) T1 22.4 ± 4.2 22.8 ± 10 5.4 ± 2.6 6.4 ± 2.05.20 ± 0.8010.0 ± 2.0a: 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.

[1]. Hopper AT, et al. Synthesis and Characterization of the Novel Rodent-Active and CNS-Penetrant P2X7 Receptor Antagonist Lu AF27139. J Med Chem. 2021;64(8):4891-4902.