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].
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| IC50& Target |
IC50: 3.3 ± 0.7 nM (AAK1), 14 nM (BIKE), 320 ± 40 nM (GAK)[1]
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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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| 分子量 |
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| 性状 |
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| Formula |
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| CAS 号 |
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| 运输条件 |
Room temperature in continental US; may vary elsewhere.
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| 储存方式 |
| Powder |
-20°C |
3 years |
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4°C |
2 years |
| In solvent |
-80°C |
6 months |
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-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 |
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请根据半岛bd体育手机客户端 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半岛bd体育手机客户端 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
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1.
请依序添加每种溶剂： 10% DMSO40%PEG3005%Tween-8045% 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。
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2.
请依序添加每种溶剂： 10% DMSO90% (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。
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3.
请依序添加每种溶剂： 10% DMSO90%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。
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以上所有助溶剂都可在本网站选购。
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