LP-935509 是一种口服有效的、选择性的、ATP 竞争性的和可透过血脑屏障的一种接头蛋白-2 相关激酶 1 (AAK1) 抑制剂，其IC50为 3.3 nM，Ki为 0.9 nM。LP-935509 也是BIKE的有效抑制剂 (IC50=14 nM) 和GAK的中度抑制剂 (IC50=320 nM)。LP-935509 具有镇痛活性。LP-935509 可用于神经性疼痛和 SARS-CoV-2 的研究。
| 生物活性 | LP-935509 is an orally active, potent, selective, ATP-competitive and brain-penetrant inhibitor ofadaptor protein-2 associated kinase 1 (AAK1)with anIC50of 3.3 nM and aKiof 0.9 nM, respectively. LP-935509 is also a potent inhibitor ofBIKE(IC50=14 nM) and a modest inhibitor ofGAK(IC50=320 nM). LP-935509 shows antinociceptive activity. LP-935509 can be used for neuropathic pain and SARS-CoV-2 research[1]. |
| IC50& Target | IC50: 3.3 ± 0.7 nM (AAK1), 14 nM (BIKE), 320 ± 40 nM (GAK)[1] |
体外研究
(In Vitro) | LP-935509 inhibits μ2 phosphorylation with an IC50value of 2.8 ± 0.4 nM, inhibits phosphorylation of a peptide derived from the μ2 protein with an IC50value of 3.3 ± 0.7 nM[1].
LP-935509 exhibits a dose-dependent inhibition of the SARS-CoV-2 S-RBD internalization into host cells[2].
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体内研究
(In Vivo) | LP-935509 (0-60 mg/kg; PO, single) causes a robust reduction in pain behavior[1].
LP-935509 (0.1-30 mg/kg; PO, single dosage) causes a dose-dependent reversal of thermal hyperalgesia in CCI model[1].
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[1].
| Animal Model: | Male C57BL/6J mice (with SNL(spinal nerve ligation) injury, n=8-10 male mice per group)[1] | | 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)[1] | | 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 ED50values ranging from 2 mg/kg to 10 mg/kg. |
| Animal Model: | Male Sprague-Dawley rats[1] | | 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. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : 50 mg/mL(126.12 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.5224 mL | 12.6122 mL | 25.2245 mL | | 5 mM | 0.5045 mL | 2.5224 mL | 5.0449 mL | | 10 mM | 0.2522 mL | 1.2612 mL | 2.5224 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.08 mg/mL (5.25 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (5.25 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.08 mg/mL (5.25 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (5.25 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。 3. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.08 mg/mL (5.25 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (5.25 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。 *以上所有助溶剂都可在本网站选购。
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