BMS-345541(free base)
目录号 : GC13926
BMS-345541(free base) 是 IKK 催化亚基的选择性抑制剂 (IKK-2 IC50=0.3 μM, IKK-1 IC50=4 μM)。 BMS-345541（游离碱）结合在 IKK 的变构位点。
Cas No.:445430-58-0
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
BMS-345541(free base) is a selective inhibitor of IKK-1 and IKK-2 with IC50 value of 4μM and 0.3μM, respectively [1].
IKK is also known as nuclear factor kappa-B kinase subunit inhibitor and involves in cytokine-activated intracellular signaling pathways. IKK-1 and IKK-2 are members of IKK family. It has been reported that IKK-2 plays a pivotal role in brain cells following a stroke [2] [3].
BMS-345541 is a potent IKK inhibitor and has a highly selective activity compared with other kinases. When tested with THP-1 monocytic cells, pre-incubation with BMS-345541 inhibited TNF-α-stimulated IKK phosphorylation and reduced a variety of cytokines production including TNF-α, IL-1β, IL-8, and IL-6 [1]. In 4 human glioma cell lines, BMS-345541 treatment significantly blocked cell proliferation (80%-95%) at the concentration of 10 μM or higher and also inhibited IL-8 expression in a dose dependent manner (IC50>2 μM) [2]. And similar result of BMS-34551 inhibition on IKK which induced cell apoptosis was verified in human melanoma cell lines SK-MEL-5, Hs 294T, and A375 [3].
In 18-22g female BALB/c mice model, administration of BMS-345541 inhibited TNF-αproduction in a dose-dependent manner, ~50% inhibition was seen when used the concentration of 10 mg/kg and near complete inhibition was seen at a dose of 100 mg/kg [1].
References:
[1]. Burke, J.R., et al., BMS-345541 is a highly selective inhibitor of I kappa B kinase that binds at an allosteric site of the enzyme and blocks NF-kappa B-dependent transcription in mice. J Biol Chem, 2003. 278(3): p. 1450-6.
[2]. Du, Z., et al., Inhibition of type I interferon-mediated antiviral action in human glioma cells by the IKK inhibitors BMS-345541 and TPCA-1. J Interferon Cytokine Res, 2012. 32(8): p. 368-77.
[3]. Yang, J., et al., BMS-345541 targets inhibitor of kappaB kinase and induces apoptosis in melanoma: involvement of nuclear factor kappaB and mitochondria pathways. Clin Cancer Res, 2006. 12(3 Pt 1): p. 950-60.
| Cell experiment [1]: | |
|
Cell lines |
THP-1 cells |
|
Preparation method |
The solubility of this compound in DMSO is >70mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
|
Reacting condition |
1-100μM for 1 h |
|
Applications |
In THP-1 cells, only the stimulus-induced phosphorylation of IκB was inhibited by BMS-345541 whereas other signal transduction cascades were unaffected. BMS-345541 inhibited IKK (Iκ B kinase) in cells in the micromolar range and was effective in THP-1 cells at inhibiting the stimulated production of a number of cytokines from THP-1 cells including TNF, IL-1, IL-8, and IL-6. |
| Animal experiment [2]: | |
|
Animal models |
18–22-g female BALB/c mice |
|
Dosage form |
2mg/kg (1 ml/kg) intravenous bolus or 10 mg/kg (5 ml/kg) peroral gavage. |
|
Application |
In BALB/c mice, BMS-345541 dose-dependently inhibited LPS (intraperitoneal)-induced serum TNF production in mice at doses in the 3 to 100 mg/kg range. Approximately 50% inhibition was observed at 10 mg/kg, near complete inhibition of serum TNF was observed at a dose of 100 mg/kg BMS-345541. |
|
Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
|
References: [1]. Burke, J.R., et al. BMS-345541 is a highly selective inhibitor of I kappa B kinase that binds at an allosteric site of the enzyme and blocks NF-kappa B-dependent transcription in mice. J Biol Chem, 2003. 278(3): p. 1450-6. | |
| Cas No. | 445430-58-0 | SDF | |
| Canonical SMILES | NCCNC1=NC2=CC=C(C)C=C2N3C1=NC=C3C | ||
| 分子式 | C14H17N5 | 分子量 | 255.32 |
| 溶解度 | ≥ 70mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 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 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 3.9167 mL | 19.5833 mL | 39.1665 mL |
| 5 mM | 0.7833 mL | 3.9167 mL | 7.8333 mL |
| 10 mM | 0.3917 mL | 1.9583 mL | 3.9167 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet