| 产品介绍 |
Rho-Kinase-IN-2 (Compound 23) 是一种具有口服活性的、选择性的和中枢神经系统 (CNS) 渗透性的 Rho激酶 (ROCK) 抑制剂 (ROCK2 IC50=3 nM)。Rho-Kinase-IN-2 可用于亨廷顿病的研究。
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| 生物活性 |
Rho-Kinase-IN-2 (Compound 23) is an orally active, selective, and central nervous system (CNS)-penetrant Rho Kinase (ROCK) inhibitor (ROCK2 IC50=3 nM). Rho-Kinase-IN-2 can be used in Huntington’s research.
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| 体外研究 |
Rho-Kinase-IN-2 (0-10 mM, 1 hour) treatment shows an increase in AKT phosphorylation and a decrease in MYPT1 phosphorylation.
西域 has not independently confirmed the accuracy of these methods. They are for reference only.
Western Blot Analysis
| Cell Line: |
A7r5 and PANC1 cells |
| Concentration: |
0-10 mM |
| Incubation Time: |
1 hour |
| Result: |
Showed concentration-dependent effects, leading to an increase in AKT phosphorylation (EC50=28 nM) and a decrease in MYPT1 phosphorylation (IC50=14 nM). |
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体内研究
(In Vivo) |
Rho-Kinase-IN-2 (oral adiministration; 10 mg/kg; 6 times; 0.5, 1, 2, 4, 8, and 12 h) treatment shows dose- and time-dependent ROCK1 and ROCK2 target engagement.
Rho-Kinase-IN-2 (oral adiministration; 10 or 20 mg/kg; QD or BID; 2 weeks) treatment shows excellent tolerability assessment.
Rho-Kinase-IN-2 (oral adiministration; 1-20 mg/kg; once) treatment shows a direct dose- and time-dependent relationship between brain exposure and MYPT1 phosphorylation status.
Rho-Kinase-IN-2 (oral adiministration; 10 or 20 mg/kg; once) treatment decreases in the mean arterial, systolic, diastolic blood pressure, and heart rate.
Rho-Kinase-IN-2 (oral adiministration; 10 mg/kg; twice a day; 90 days) treatment leads to lower-than-expected brain concentrations.
西域 has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: |
Male C57BL/6 mice |
| Dosage: |
10 mg/kg |
| Administration: |
Oral adiministration; 10 mg/kg; 6 times; 0.5, 1, 2, 4, 8, and 12 h |
| Result: |
Observed dose- and time-dependent ROCK1 and ROCK2 TE, with a free brain KiNativ ROCK1 and ROCK2 IC50=∼6 nM. |
| Animal Model: |
3−4 months old heterozygote Q175DN KI and wild-type littermate mice |
| Dosage: |
10 or 20 mg/kg |
| Administration: |
Oral adiministration; 10 or 20 mg/kg; once a day or twice a day; 2 weeks |
| Result: |
Scored neurological index normally at all doses although a slight loss in bodyweight (∼2%) in the 20 mg/kg treatment group. |
| Animal Model: |
Heterozygote HTT zQ175DN knock-in mice |
| Dosage: |
1-20 mg/kg |
| Administration: |
Oral adiministration; 1-20 mg/kg; once |
| Result: |
Remained over MYPT1 IC50 for over 2 h of the free brain at 10 mg/kg, and observed the dose- and time-dependent inhibition of MYPT1 phosphorylation in the striatum following acute in vivo dosing. |
| Animal Model: |
CD1 mice |
| Dosage: |
10 and 20 mg/kg |
| Administration: |
Oral adiministration; 10 or 20 mg/kg; once |
| Result: |
Observed the decreases in the mean arterial (maximum change of 61.0 ± 8.5 mmHg from baseline), systolic (maximum change of 59.5 ± 8.4 mmHg from baseline), diastolic blood pressure (maximum change of 56.4 ± 9.0 mmHg from baseline), and heart rate (maximum change from predose of 107 bpm) when compared to the control group from ∼0.5 to 2 h post dose. |
| Animal Model: |
Heterozygote Q175DN KI mouse model of HD |
| Dosage: |
10 mg/kg |
| Administration: |
Oral adiministration; 10 mg/kg; twice a day; 90 days |
| Result: |
Led to lower-than-expected brain concentrations compared to single dosing. |
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| 体内研究 |
Rho-Kinase-IN-2 (oral adiministration; 10 mg/kg; 6 times; 0.5, 1, 2, 4, 8, and 12 h) treatment shows dose- and time-dependent ROCK1 and ROCK2 target engagement.
Rho-Kinase-IN-2 (oral adiministration; 10 or 20 mg/kg; QD or BID; 2 weeks) treatment shows excellent tolerability assessment.
Rho-Kinase-IN-2 (oral adiministration; 1-20 mg/kg; once) treatment shows a direct dose- and time-dependent relationship between brain exposure and MYPT1 phosphorylation status.
Rho-Kinase-IN-2 (oral adiministration; 10 or 20 mg/kg; once) treatment decreases in the mean arterial, systolic, diastolic blood pressure, and heart rate.
Rho-Kinase-IN-2 (oral adiministration; 10 mg/kg; twice a day; 90 days) treatment leads to lower-than-expected brain concentrations.
西域 has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: |
Male C57BL/6 mice |
| Dosage: |
10 mg/kg |
| Administration: |
Oral adiministration; 10 mg/kg; 6 times; 0.5, 1, 2, 4, 8, and 12 h |
| Result: |
Observed dose- and time-dependent ROCK1 and ROCK2 TE, with a free brain KiNativ ROCK1 and ROCK2 IC50=∼6 nM. |
| Animal Model: |
3−4 months old heterozygote Q175DN KI and wild-type littermate mice |
| Dosage: |
10 or 20 mg/kg |
| Administration: |
Oral adiministration; 10 or 20 mg/kg; once a day or twice a day; 2 weeks |
| Result: |
Scored neurological index normally at all doses although a slight loss in bodyweight (∼2%) in the 20 mg/kg treatment group. |
| Animal Model: |
Heterozygote HTT zQ175DN knock-in mice |
| Dosage: |
1-20 mg/kg |
| Administration: |
Oral adiministration; 1-20 mg/kg; once |
| Result: |
Remained over MYPT1 IC50 for over 2 h of the free brain at 10 mg/kg, and observed the dose- and time-dependent inhibition of MYPT1 phosphorylation in the striatum following acute in vivo dosing. |
| Animal Model: |
CD1 mice |
| Dosage: |
10 and 20 mg/kg |
| Administration: |
Oral adiministration; 10 or 20 mg/kg; once |
| Result: |
Observed the decreases in the mean arterial (maximum change of 61.0 ± 8.5 mmHg from baseline), systolic (maximum change of 59.5 ± 8.4 mmHg from baseline), diastolic blood pressure (maximum change of 56.4 ± 9.0 mmHg from baseline), and heart rate (maximum change from predose of 107 bpm) when compared to the control group from ∼0.5 to 2 h post dose. |
| Animal Model: |
Heterozygote Q175DN KI mouse model of HD |
| Dosage: |
10 mg/kg |
| Administration: |
Oral adiministration; 10 mg/kg; twice a day; 90 days |
| Result: |
Led to lower-than-expected brain concentrations compared to single dosing. |
|
|---|
| 体内研究 |
Rho-Kinase-IN-2 (oral adiministration; 10 mg/kg; 6 times; 0.5, 1, 2, 4, 8, and 12 h) treatment shows dose- and time-dependent ROCK1 and ROCK2 target engagement.
Rho-Kinase-IN-2 (oral adiministration; 10 or 20 mg/kg; QD or BID; 2 weeks) treatment shows excellent tolerability assessment.
Rho-Kinase-IN-2 (oral adiministration; 1-20 mg/kg; once) treatment shows a direct dose- and time-dependent relationship between brain exposure and MYPT1 phosphorylation status.
Rho-Kinase-IN-2 (oral adiministration; 10 or 20 mg/kg; once) treatment decreases in the mean arterial, systolic, diastolic blood pressure, and heart rate.
Rho-Kinase-IN-2 (oral adiministration; 10 mg/kg; twice a day; 90 days) treatment leads to lower-than-expected brain concentrations.
西域 has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: |
Male C57BL/6 mice |
| Dosage: |
10 mg/kg |
| Administration: |
Oral adiministration; 10 mg/kg; 6 times; 0.5, 1, 2, 4, 8, and 12 h |
| Result: |
Observed dose- and time-dependent ROCK1 and ROCK2 TE, with a free brain KiNativ ROCK1 and ROCK2 IC50=∼6 nM. |
| Animal Model: |
3−4 months old heterozygote Q175DN KI and wild-type littermate mice |
| Dosage: |
10 or 20 mg/kg |
| Administration: |
Oral adiministration; 10 or 20 mg/kg; once a day or twice a day; 2 weeks |
| Result: |
Scored neurological index normally at all doses although a slight loss in bodyweight (∼2%) in the 20 mg/kg treatment group. |
| Animal Model: |
Heterozygote HTT zQ175DN knock-in mice |
| Dosage: |
1-20 mg/kg |
| Administration: |
Oral adiministration; 1-20 mg/kg; once |
| Result: |
Remained over MYPT1 IC50 for over 2 h of the free brain at 10 mg/kg, and observed the dose- and time-dependent inhibition of MYPT1 phosphorylation in the striatum following acute in vivo dosing. |
| Animal Model: |
CD1 mice |
| Dosage: |
10 and 20 mg/kg |
| Administration: |
Oral adiministration; 10 or 20 mg/kg; once |
| Result: |
Observed the decreases in the mean arterial (maximum change of 61.0 ± 8.5 mmHg from baseline), systolic (maximum change of 59.5 ± 8.4 mmHg from baseline), diastolic blood pressure (maximum change of 56.4 ± 9.0 mmHg from baseline), and heart rate (maximum change from predose of 107 bpm) when compared to the control group from ∼0.5 to 2 h post dose. |
| Animal Model: |
Heterozygote Q175DN KI mouse model of HD |
| Dosage: |
10 mg/kg |
| Administration: |
Oral adiministration; 10 mg/kg; twice a day; 90 days |
| Result: |
Led to lower-than-expected brain concentrations compared to single dosing. |
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| 性状 | Solid |
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| 溶解性数据 |
In Vitro:
DMSO : 50 mg/mL (134.25 mM; Need ultrasonic)
配制储备液
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浓度
溶剂体积
质量
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1 mg |
5 mg |
10 mg |
| 1 mM |
2.6850 mL |
13.4250 mL |
26.8500 mL |
| 5 mM |
0.5370 mL |
2.6850 mL |
5.3700 mL |
| 10 mM |
0.2685 mL |
1.3425 mL |
2.6850 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°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 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 mg/mL (5.37 mM); Clear solution
此方案可获得 ≥ 2 mg/mL (5.37 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 20.0 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% DMSO 90% (20% SBE-β-CD in saline) Solubility: ≥ 2 mg/mL (5.37 mM); Clear solution
此方案可获得 ≥ 2 mg/mL (5.37 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 20.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 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% DMSO 90% corn oil Solubility: ≥ 2 mg/mL (5.37 mM); Clear solution
此方案可获得 ≥ 2 mg/mL (5.37 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 20.0 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 西域 网站选购。
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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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| 参考文献 | |
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