Lu AF27139

Lu AF27139

L649989-5mg

5mg

≥99%

-20°C储存

超低温冰袋运输

Lu AF27139 is a potent, selective, and orally active antagonist of P2X7 receptor ( IC 50 s of 12 and 2.4 nM for human and rat, K i s 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 In Vitro 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 IC 50 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 IC 50 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. MCE has not independently confirmed the accuracy of these methods. They are for reference only. In Vivo 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 . dose C u, plasma (nM) a C u, brain (nM) a C u, spinal cord (nM) a (mg/kg, po) (1 h) (2 h) (1 h) (2 h) (1 h) (2 h) T 1 22.4 ± 4.2 22.8 ± 10 5.4 ± 2.6 6.4 ± 2.0 5.20 ± 0.80 10.0 ± 2.0 a: Free plasma, brain, and spinal cord concentrations of Lu AF27139 in rat were determined by the formula (Ct*f u ), where Ct is the total tissue (plasma, brain, or spinal cord) drug concentration and f u is the fraction unbound in these tissues as determined by ex vivo equilibrium dialysis. Values are expressed as mean ± SEM for n = 3 animals. f u , plasma = 0.02 ± 0.00, f u , spinal cord = 0.07 ± 0.03, and f u , brain = 0.09 ± 0.03. Values are expressed as mean ± SEM for n ≥ 3 experiments. MCE has not independently confirmed the accuracy of these methods. They are for reference only. 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. Form:Solid IC50& Target:P2X7

Lu AF27139 是一种强效、选择性和口服活性的 P2X7 受体拮抗剂（人和大鼠的 IC 50 s 分别为 12 和 2.4 nM，小鼠、人和大鼠的 K i s 分别为 22、54 和 13 nM）。Lu AF27139 具有鼠药活性和中枢神经系统穿透性。L

2097117-06-9

C21H19ClF3N5O2S

497.92 g/mol

ClC(C=C1)=CC=C1[C@H](N2CCOCC2)CNC(C3=C(C(F)(F)F)N=C(C4=NC=CC=N4)S3)=O

DMSO : 125 mg/mL (251.04 mM; Need ultrasonic)