LP-935509

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

LP-935509 是一种有效的、选择性的、脑渗透性的接头蛋白 2 相关激酶 1 (AAK1) 抑制剂，IC50 为 3.3 nM。

LP-935509 is a?potent, selective and brain-penetrant adapter protein-2 associated kinase 1 (AAK1) inhibitor with IC50 of 3.3 nM; inhibited μ2 protein phosphorylation in HEK293 cells overexpressing human AAK1 with IC50 of 2.8 nM; also potent inhibits closely related BIKE and GAK with IC50 of 14 nM and 320 nM, respectively in a panel of 389 kinases; reduces pain response in phase II formalin and reverses fully established pain behavior in vivo.

LP-935509 inhibits μ2 phosphorylation with an IC50 value of 2.8 ± 0.4 nM, inhibits phosphorylation of a peptide derived from the μ2 protein with an IC50 value of 3.3 ± 0.7 nM.LP-935509 exhibits a dose-dependent inhibition of the SARS-CoV-2 S-RBD internalization into host cells.

LP-935509 (0-60 mg/kg; PO, single) causes a robust reduction in pain behavior.?LP-935509 (0.1-30 mg/kg; PO, single dosage) causes a dose-dependent reversal of thermal hyperalgesia in CCI model.?LP-935509 (IV (1 mg/kg) or orally (10 mg/kg); once) has 100% oral bioavailability and a plasma half life of 3.6 hours. Animal Model:Male C57BL/6J mice (with SNL(spinal nerve ligation) injury, n=8-10 male mice per group)Dosage:0, 10, 30 and 60 mg/kg (10 ml/kg) Administration:PO, single Result:Caused a dose-dependent reduction in phase II paw flinches that was significantly lower than the vehicle-treated animals; exhibited a dose-dependent reversal of the mechanical allodynia; Caused a robust reduction in pain behavior.Animal Model:Male Sprague-Dawley rats (CCI (chronic constriction injury)-operated rats) Dosage:0, 0.1, 0.3, 1, 3, 10, or 30 mg/kg Administration:PO, two daily, for 5 days Result:Caused a dose-dependent reversal of thermal hyperalgesia, cold allodynia, mechanical allodynia, and mechanical hyperalgesia in CCI animals. Reversed the behavioral deficits, with ED50 values ranging from 2 mg/kg to 10 mg/kg.Animal Model:Male Sprague-Dawley rats Dosage:1 mg/kg (IV), 10 mg/kg (PO) Administration:IV, PO; once (Pharmacokinetic Analysis)Result:Had 100% oral bioavailability and a plasma half life of 3.6 hours; The Cmax for the 10 mg/kg oral dose was 5.2 μM at 0.5-hour postdose; had a plasma-free fraction of 2.6% in mice. Brain drug levels exceeded plasma drug levels with a brain/plasma drug ratio typically between 3 and 4, showing that LP-935509 was highly brain-penetrant.

LP935509 | LP 935509

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AAK1

AAK1

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1454555-29-3

396.451

C20H24N6O3

>98% (HPLC)

In Vitro:?DMSO : 50 mg/mL (126.12 mM)

O=C(N1CCN(C2=NC3=C(C4=CC=CN=C4OC)C=NN3C=C2)CC1)OC(C)C

isopropyl 4-(3-(2-methoxypyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)piperazine-1-carboxylate

(-20℃)

With Ice Pack

≥ 2 years