Rho-Kinase-IN-2

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Rho-Kinase-IN-2

本产品不向个人销售，仅用作科学研究，不用于任何人体实验及非科研性质的动物实验。

CAS NO:

2573071-18-6

包装与价格：

包装	价格(元)
5mg	电议
10mg	电议
25mg	电议
50mg	电议
100mg	电议
200mg	电议

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 (ROCK2IC₅₀=3 nM)。Rho-Kinase-IN-2 可用于亨廷顿病的研究。

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 (ROCK2IC₅₀=3 nM). Rho-Kinase-IN-2 can be used in Huntington’s research^[1].

IC₅₀& Target

ROCK2

3 nM (IC₅₀)

体外研究
(In Vitro)

Rho-Kinase-IN-2 (0-10 mM, 1 hour) treatment shows an increase in AKT phosphorylation and a decrease in MYPT1 phosphorylation^[1].

Western Blot Analysis^[1]

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).

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^[1].
Rho-Kinase-IN-2 (oral adiministration; 10 or 20 mg/kg; QD or BID; 2 weeks) treatment shows excellent tolerability assessment^[1].
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^[1].
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^[1].
Rho-Kinase-IN-2 (oral adiministration; 10 mg/kg; twice a day; 90 days) treatment leads to lower-than-expected brain concentrations^[1].

Animal Model:	Male C57BL/6 mice^[1]
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^[1]
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^[1]
Dosage:	1-20 mg/kg
Administration:	Oral adiministration; 1-20 mg/kg; once
Result:	Remained over MYPT1 IC₅₀for 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^[1]
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^[1]
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.

分子量

372.44

性状

Solid

Formula

C₂₀H₂₅FN₄O₂

CAS 号

2573071-18-6

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

溶解性数据

In Vitro:

DMSO : 50 mg/mL(134.25 mM;Need ultrasonic)

配制储备液

浓度溶剂体积质量

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℃, 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 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。
将 0.9 g 氯化钠，完全溶解于 100 mL ddH2O 中，得到澄清透明的生理盐水溶液
2.
请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin 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 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。
将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
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本网站选购。