CZC-25146|cas:1191911-26-8|西域试剂

CZC-25146,98.85%

产品编号：Bellancom-15800A| CAS NO：1191911-26-8| 分子式：C₂₂H₂₅FN₆O₄S| 分子量：488.54

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货号	价格	库存与货期
Bellancom-15800A	￥800.00	杭州北京（现货）
Bellancom-15800A	￥1400.00	杭州北京（现货）
Bellancom-15800A	￥5600.00	杭州北京（现货）
Bellancom-15800A	￥9800.00	杭州北京（现货）

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CZC-25146

产品介绍

CZC-25146 是一种有效且具有口服活性的 LRRK2 抑制剂，对野生型 LRRK2 和突变型 LRRK2 G2019S 的 IC₅₀ 分别为 4.76 nM 和 6.87 nM。也抑制激酶 PLK4、GAK、TNK1、CAMKK2 和 PIP4K2C。CZC-25146 能在体外抑制突变 LRRK2 诱导的神经元损伤。CZC-25146 在小鼠体内表现出相对较好的药代动力学特性。CZC-25146 还能增加正常的 α-1 抗胰蛋白酶 (AAT) 的分泌，减少炎症细胞因子。CZC-25146 可用于帕金森病和肝病的研究。

生物活性

CZC-25146 is a potent and orally active LRRK2 inhibitor with IC₅₀ values of 4.76 nM and 6.87 nM for wild-type LRRK2 and G2019S LRRK2, respectively. CZC-25146 inhibits PLK4, GAK, TNK1, CAMKK2 and PIP4K2C as well. CZC-25146 prevents mutant LRRK2-induced injury of neurons in vitro. CZC-25146 exhibits relatively favorable pharmacokinetic properties in mice. CZC-25146 can increase normal α-1-antitrypsin (AAT) secretion and reduce inflammatory cytokines. CZC-25146 can be used to research Parkinson's disease and liver diseases.

体外研究

CZC-25146 (0.01-5 μM; 7 days) does not cause cytotoxicity in human cortical neurons, nor blocking neuronal development.
CZC-25146 (0.01-5 μM; 2 days) potently attenuates G2019S LRRK2-mediated toxicity in primary rodent neurons in a concentration-dependent manner with an EC₅₀ of ~100 nM.
CZC-25146 (0.06-1000 nM) rescues LRRK2 G2019S-induced neurite defects in primary human neurons in a dose-dependent manner.
CZC-25146 (14.3 and 28.6 μM; 48 h) markedly reduces The mutant AAT encoded by the Z allele (ATZ) polymer load and restores AAT secretion in iPSC-Hepatocyte, without compromising cell viability.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Cytotoxicity Assay

Cell Line:	Human cortical neurons
Concentration:	0.01, 0.1, 1 and 5 μM
Incubation Time:	7 days
Result:	Did not cause cytotoxicity in human cortical neurons at concentrations below 5 μM over a seven-day treatment in culture, nor did it block neuronal development.

体内研究
(In Vivo)

CZC-25146 (250 mg/kg; p.o.; 14 days) reduces the ATZ polymer levels in over expressing human polymeric ATZ mice.
CZC-25146 (1 mg/kg for i.v.; 5 mg/kg for p.o.; single dosage) exhibits relatively good pharmacokinetic properties and an extensive distribution throughout animal body following intravenous injection into mice.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	Genetically modified male mice (6 weeks; over expressing human polymeric ATZ)
Dosage:	250 mg/kg
Administration:	p.o.; 14 days
Result:	Dramatically and reproducibly reduced the ATZ polymer levels with an overall reduction from 60% in the control group to 37%.

Animal Model:

Male CD-1 mice

Dosage:

1 mg/kg for i.v.; 5 mg/kg for p.o.

Administration:

i.v. and p.o.; single dosage

Result:

Pharmacokinetic Parameters of CZC-25146 in male CD-1 mice.

	i.v. (1 mg/kg)	p.o. (5 mg/kg)
CL (L/h/kg)	2.3
V_ss (L/kg)	5.4
t_1/2 (h)	1.6	1
t_max (h)	0	0.25
C_max (ng/mL)	154	1357
AUC_last (ng/mL·h)	419	2878
AUC_inf (ng/mL·h)	434	2894
F (%)		133

体内研究

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	Genetically modified male mice (6 weeks; over expressing human polymeric ATZ)
Dosage:	250 mg/kg
Administration:	p.o.; 14 days
Result:	Dramatically and reproducibly reduced the ATZ polymer levels with an overall reduction from 60% in the control group to 37%.

Animal Model:

Male CD-1 mice

Dosage:

1 mg/kg for i.v.; 5 mg/kg for p.o.

Administration:

i.v. and p.o.; single dosage

Result:

Pharmacokinetic Parameters of CZC-25146 in male CD-1 mice.

	i.v. (1 mg/kg)	p.o. (5 mg/kg)
CL (L/h/kg)	2.3
V_ss (L/kg)	5.4
t_1/2 (h)	1.6	1
t_max (h)	0	0.25
C_max (ng/mL)	154	1357
AUC_last (ng/mL·h)	419	2878
AUC_inf (ng/mL·h)	434	2894
F (%)		133

体内研究

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	Genetically modified male mice (6 weeks; over expressing human polymeric ATZ)
Dosage:	250 mg/kg
Administration:	p.o.; 14 days
Result:	Dramatically and reproducibly reduced the ATZ polymer levels with an overall reduction from 60% in the control group to 37%.

Animal Model:

Male CD-1 mice

Dosage:

1 mg/kg for i.v.; 5 mg/kg for p.o.

Administration:

i.v. and p.o.; single dosage

Result:

Pharmacokinetic Parameters of CZC-25146 in male CD-1 mice.

	i.v. (1 mg/kg)	p.o. (5 mg/kg)
CL (L/h/kg)	2.3
V_ss (L/kg)	5.4
t_1/2 (h)	1.6	1
t_max (h)	0	0.25
C_max (ng/mL)	154	1357
AUC_last (ng/mL·h)	419	2878
AUC_inf (ng/mL·h)	434	2894
F (%)		133

性状

Solid

溶解性数据

In Vitro:

DMSO : ≥ 46 mg/mL (94.16 mM)

* "≥" means soluble, but saturation unknown.

配制储备液

浓度溶剂体积质量	1 mg	5 mg	10 mg

1 mM	2.0469 mL	10.2346 mL	20.4692 mL
5 mM	0.4094 mL	2.0469 mL	4.0938 mL
10 mM	0.2047 mL	1.0235 mL	2.0469 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: ≥ 2.5 mg/mL (5.12 mM); Clear solution

此方案可获得 ≥ 2.5 mg/mL (5.12 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 25.0 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% corn oil
Solubility: ≥ 2.5 mg/mL (5.12 mM); Clear solution

此方案可获得 ≥ 2.5 mg/mL (5.12 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 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。