1. MAPK/ERK Pathway
  2. JNK
  3. CC-401 hydrochloride

CC-401 hydrochloride  (Synonyms: CC401 HCl)

目录号: HY-13022 纯度: 99.46%
COA 产品使用指南

CC-401 hydrochloride 是一种有效的 JNK 抑制剂,Ki 为 25 到 50 nM。

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CC-401 hydrochloride Chemical Structure

CC-401 hydrochloride Chemical Structure

CAS No. : 1438391-30-0

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Free Sample (0.1 - 0.2 mg)   Apply now  
10 mM * 1 mL in DMSO ¥990
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5 mg ¥900
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10 mg ¥1400
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25 mg ¥2800
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50 mg ¥4300
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100 mg ¥6200
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Other Forms of CC-401 hydrochloride:

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  • 生物活性

  • 实验参考方法

  • 纯度 & 产品资料

  • 参考文献

生物活性

CC-401 hydrochloride is a potent inhibitor of all three forms of JNK with Ki of 25 to 50 nM.

IC50 & Target[1]

JNK

25-50 nM (Ki)

体外研究
(In Vitro)

CC-401 hydrochloride 对 JNK 的选择性至少是其他相关激酶的 40 倍,包括 p38、细胞外信号调节激酶 (ERK)、κB 激酶抑制剂 (IKK2)、蛋白激酶 C、Lck、70 的 zeta 相关蛋白kDa (ZAP70)。在基于细胞的测定中,CC-401 hydrochloride (1 - 5 μM) 特异性抑制 JNK。CC-401 hydrochloride,一种小分子,是所有三种 JNK 亚型的特异性抑制剂。CC-401 hydrochloride 竞争性结合 JNK 中的 ATP 结合位点,从而抑制转录因子 c-Jun 的 N 末端激活域的磷酸化。使用 HK-2 人肾小管上皮细胞系的渗透压在体外测试了该抑制剂的特异性。CC-401 hydrochloride 以剂量依赖性方式抑制 Sorbitol 诱导的 c-Jun 磷酸化。然而,CC-401 hydrochloride 不会阻止 Sorbitol 诱导的 JNK、p38 或 ERK磷酸化[1]

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

体内研究
(In Vivo)

与对照组相比,Bevazicumab 和 Oxaliplatin 处理适度诱导 p-JNK 染色,并且在 CC-401 处理的样品中 p-cJun 含量显著降低,与有效的 JNK 抑制一致。 与 CC-401 联合治疗时 DNA 损伤适度升高[2]。第 7 天至第 24 天的 CC-401 处理减缓了蛋白尿的进展,与第 14 天和第 21 天的无治疗组和载体组相比显著降低。但是,与第 5 天的蛋白尿相比,在第 21 天时 CC-401 处理的大鼠蛋白尿程度仍然有所增加 。载体组和未治疗组在第 24 天出现肾功能损害,表现为血清肌酐升高,可通过 CC-401 处理来防止[3]

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

Clinical Trial
分子量

424.93

Formula

C22H25ClN6O

CAS 号
性状

固体

颜色

White to off-white

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

溶解性数据
In Vitro: 

DMSO 中的溶解度 : 100 mg/mL (235.33 mM; 超声助溶; 吸湿的 DMSO 对产品的溶解度有显著影响,请使用新开封的 DMSO)

H2O 中的溶解度 : 12.5 mg/mL (29.42 mM; 超声助溶)

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 2.3533 mL 11.7666 mL 23.5333 mL
5 mM 0.4707 mL 2.3533 mL 4.7067 mL
查看完整储备液配制表

* 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 (sealed storage, away from moisture)。-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。

* 备注:如您选择水作为储备液,请稀释至工作液后,再用 0.22 μm 的滤膜过滤除菌后使用。

  • 摩尔计算器

  • 稀释计算器

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

质量
=
浓度
×
体积
×
分子量 *

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

浓度 (start)

C1

×
体积 (start)

V1

=
浓度 (final)

C2

×
体积 (final)

V2

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

  • 方案 一

    请依序添加每种溶剂: 10% DMSO    40% PEG300    5% Tween-80    45% Saline

    Solubility: ≥ 2.5 mg/mL (5.88 mM); 澄清溶液

    此方案可获得 ≥ 2.5 mg/mL(饱和度未知)的澄清溶液。

    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;再向上述体系中加入 50 μL Tween-80,混合均匀;然后再继续加入 450 μL 生理盐水 定容至 1 mL

    生理盐水的配制:将 0.9 g 氯化钠,溶解于 ddH₂O 并定容至 100 mL,可以得到澄清透明的生理盐水溶液。
  • 方案 二

    请依序添加每种溶剂: 10% DMSO    90% (20% SBE-β-CD in Saline)

    Solubility: ≥ 2.5 mg/mL (5.88 mM); 澄清溶液

    此方案可获得 ≥ 2.5 mg/mL(饱和度未知)的澄清溶液。

    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 20% 的 SBE-β-CD 生理盐水水溶液 中,混合均匀。

    20% SBE-β-CD in Saline 的配制(4°C,储存一周):2 g SBE-β-CD(磺丁基醚 β-环糊精)粉末定容于 10 mL 的生理盐水中,完全溶解至澄清透明。

以下溶解方案,请直接配置工作液。建议现用现配,在短期内尽快用完。 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。

  • 方案 一

    请依序添加每种溶剂: PBS

    Solubility: 14.29 mg/mL (33.63 mM); 澄清溶液; 超声助溶 (<60°C)

动物溶解方案计算器
请输入动物实验的基本信息:

给药剂量

mg/kg

动物的平均体重

g

每只动物的给药体积

μL

动物数量

由于实验过程有损耗,建议您多配一只动物的量
请输入您的动物体内配方组成:
%
DMSO +
+
%
Tween-80 +
%
Saline
如果您的动物是免疫缺陷鼠或者体弱鼠,建议 DMSO 中的在最后工作液体系中的占比尽量不超过 2%。
方案所需 助溶剂 包括:DMSO ,均可在 MCE 网站选购。 Tween 80,均可在 MCE 网站选购。
计算结果
工作液所需浓度 : mg/mL
储备液配制方法 : mg 药物溶于 μL  DMSO(母液浓度为 mg/mL)。

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

您所需的储备液浓度超过该产品的实测溶解度,以下方案仅供参考,如有需要,请与 MCE 中国技术支持联系。
动物实验体内工作液的配制方法 : 取 μL DMSO 储备液,加入 μL  μL ,混合均匀至澄清,再加 μL Tween 80,混合均匀至澄清,再加 μL 生理盐水
连续给药周期超过半月以上,请谨慎选择该方案。
请确保第一步储备液溶解至澄清状态,从左到右依次添加助溶剂。您可采用超声加热 (超声清洗仪,建议频次 20-40 kHz),涡旋吹打等方式辅助溶解。
纯度 & 产品资料

纯度: 99.46%

参考文献
Cell Assay
[1]

Human HK-2 proximal tubular epithelial cells are cultured in DMEM/F12 media supplemented with 10% FCS, 10 ng/mL EGF, and 10 μg/mL bovine pituitary extract. For Western blot studies, cells are seeded into six-well plates and allowed to adhere overnight, and medium is changed to DMEM/F12 supplemented with only 0.5% FCS for 24 h, by which time cells are confluent. CC-401 is prepared in citric acid (pH 5.5) and added to the confluent cells 1 h before the addition of 300 mM sorbitol, and cells are harvested 30 min later using urea-RIPA buffer. Three experiments are performed, each with two replicates per condition. For ELISA experiments, HK-2 cells are seeded into 24-well plates, allowed to adhere overnight, cultured in DMEM/F12 with 0.5% FCS for 24 h, and then incubated with CC-401 or vehicle for 60 min before stimulation with 1 μM Angiotensin II (AngII). Supernatants are harvested 48 h later and assayed for TGF-β1 content using a commercial ELISA kit. Three experiments are performed, each using six replicates per condition[1].

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

Animal Administration
[2][3]

Mice[2]
To assess the efficacy of JNK signaling inhibition by CC-401 in anti-angiogenic and Oxaliplatin combination therapy in a mouse xenograft model, adult (8-10 weeks of age) female severe combined immunodeficient mice (C.B.17 SCID) are used. To generate tumors, HT29 cells (1×106 cells) are injected subcutaneously into the left flank of the mice. When the tumors reached approximately 200 mm3, mice are divided into eight groups (eight mice per group) for treatment with Bevacizumab, Oxaliplatin, CC401, and the appropriate combinations of Bevacizumab, Oxaliplatin and CC-401. Mice in the Bevacizumab treatment group receive 5 mg/kg of Bevacizumab by intraperitoneal injection every 3 days for 21 days. The Oxaliplatin treatment group is injected intraperitoneally with 5 mg/kg Oxaliplatin per week for 2 weeks. The CC-401 treatment group is injected intraperitoneally 25 mg/kg for every 3 days. The combination treatment groups receive Bevacizumab (every 3 days, 5 mg/kg), Oxaliplatin (weekly for 2 weeks, 5 mg/kg), and CC-401 (every 3 days, 25 mg/kg). The control group receive saline intraperitoneally. Tumor volume and body weight are measured every 3 days. Tumor volume is calculated. Tumor growth delay is calculated as the difference in the time for control and treated tumors to grow from 200 to 800 mm3. For tumor growth delay calculations, mice are continued to receive treatments till the tumor volume reached 800 mm3. For immunohistochemistry mice are sacrificed after treatments on day 9 for tumor processing and staining.
Rats[3]
Female WKY rats (180-220 g) are used. Groups of 9 or 10 rats are immunized by subcutaneous injection of 5 mg of sheep IgG in Freund's complete adjuvant followed 5 days later (termed day 0) by a tail vein injection of sheep anti-rat GBM serum. In this study, CC-401 (200 mg/kg/b.i.d. by oral gavage) or vehicle (sodium citrate) treatment is initiated in groups of 9 or 10 rats at 7 days after anti-GBM serum administration and continued twice daily thereafter until animals are killed at day 24. Additional groups of rats without treatment are killed at day 7 or day 24 after anti-GBM serum injection as controls. Animals are housed in metabolic cages for 22 hours to collect urine on days 5, 14, and 21. Blood is collected at the time of death. Analysis of serum creatinine and urinary protein are performed.

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

参考文献

CC-401 hydrochloride 相关分类

完整储备液配制表

* 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 (sealed storage, away from moisture)。-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。

可选溶剂 浓度 溶剂体积 质量 1 mg 5 mg 10 mg 25 mg
H2O / DMSO 1 mM 2.3533 mL 11.7666 mL 23.5333 mL 58.8332 mL
5 mM 0.4707 mL 2.3533 mL 4.7067 mL 11.7666 mL
10 mM 0.2353 mL 1.1767 mL 2.3533 mL 5.8833 mL
15 mM 0.1569 mL 0.7844 mL 1.5689 mL 3.9222 mL
20 mM 0.1177 mL 0.5883 mL 1.1767 mL 2.9417 mL
25 mM 0.0941 mL 0.4707 mL 0.9413 mL 2.3533 mL
DMSO 30 mM 0.0784 mL 0.3922 mL 0.7844 mL 1.9611 mL
40 mM 0.0588 mL 0.2942 mL 0.5883 mL 1.4708 mL
50 mM 0.0471 mL 0.2353 mL 0.4707 mL 1.1767 mL
60 mM 0.0392 mL 0.1961 mL 0.3922 mL 0.9806 mL
80 mM 0.0294 mL 0.1471 mL 0.2942 mL 0.7354 mL
100 mM 0.0235 mL 0.1177 mL 0.2353 mL 0.5883 mL

* 备注:如您选择水作为储备液,请稀释至工作液后,再用 0.22 μm 的滤膜过滤除菌后使用。

Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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产品名称:
CC-401 hydrochloride
目录号:
HY-13022
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