| A-1210477MCL-1 inhibitor |
Sample solution is provided at 25 µL, 10mM.
Quality Control & MSDS
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- Purity = 98.05%
- COA (Certificate Of Analysis)
- HPLC
- NMR (Nuclear Magnetic Resonance)
- MSDS (Material Safety Data Sheet)
- Datasheet
Chemical structure
Related Biological Data
Related Biological Data
| Kinase experiment [1]: | |
Binding affinity assays | TR-FRET-binding affinity assays were performed for BCL-2, BCL-XL and MCL-1 in 4.52 mM monobasic potassium phosphate, 15.48 mM dibasic potassium phosphate, 1 mM sodium EDTA, 0.05% Pluronic F-68 detergent, 50 mM sodium chloride and 1 mM DTT (pH 7.5). For MCL-1 assays, GST-tagged MCL-1 (1 nM) was mixed with 100 nM f-Bak, 1 nM Tb-labeled anti-GST antibody and compound at room temperature for 60 mins. Fluorescence was measured on an Envision plate reader using a 340/35 nm excitation filter and 520/525 (f-Bak) and 495/510 nm (Tb-labeled anti-GST antibody) emission filters. |
| Cell experiment [1]: | |
Cell lines | H929 cells |
Preparation method | This compound is soluble in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
Reacting condition | 0 ~ 30 μM; 4 hrs |
Applications | In H929 cells, A-1210477 bound selectively and strongly to MCL-1, and reduced the amount of BIM co-immunoprecipitated with MCL-1 in a dose-dependent manner with an IC50 value in the low-μM range. |
References: [1]. Leverson JD, Zhang H, Chen J, et al. Potent and selective small-molecule MCL-1 inhibitors demonstrate on-target cancer cell killing activity as single agents and in combination with ABT-263 (navitoclax). Cell death & disease, 2015, 6(1): e1590. | |
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| Cas No. | 1668553-26-1 | SDF | Download SDF |
| Synonyms | N/A | ||
| Chemical Name | 7-(5-((4-(4-(N,N-dimethylsulfamoyl)piperazin-1-yl)phenoxy)methyl)-1,3-dimethyl-1H-pyrazol-4-yl)-1-(2-morpholinoethyl)-3-(3-(naphthalen-1-yloxy)propyl)-1H-indole-2-carboxylic acid | ||
| Canonical SMILES | CC1=NN(C(COC2=CC=C(N3CCN(S(N(C)C)(=O)=O)CC3)C=C2)=C1C4=CC=CC(C(CCCOC5=CC=CC6=CC=CC=C65)=C7C(O)=O)=C4N7CCN8CCOCC8)C | ||
| Formula | C46H55N7O7S | M.Wt | 850.04 |
| Solubility | <1.7mg l="" in="" dmso=""> | Storage | Store at -20°C |
| Shipping Condition | Evaluation sample solution : ship with blue ice.All other available size:ship with RT , or blue ice upon request | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. | ||
A-1210477 is an effective and specific MCL-1 inhibitor with an EC50 value below 5 µmol/L [1]. Selectively, it binds to MCL-1 with an affinity of 0.45 nM [2].
MCL-1, an anti-apoptotic Bcl-2 family member, is an anti-apoptotic protein. It is a key regulator of cancer cell survival [3, 4].
In MCL-1-dependent SVEC cells, treatment with A-1210477 at varying doses, induced cell death in a dose-dependent manner. SYTOX Green exclusion and live-cell imaging were used to determine cell viability. In line with increased potency, cell death was more rapidly induced by A-1210477. To examine the selectivity of A-1210477 for targeting Bcl-2 family members, BcL-xL-, BcL-2-, and MCL-1-dependent SVEC cells were treated with A-1210477. A-1210477 only killed MCL-1-dependent cells. Compared with UMI-77, A-1210477 showed greater potency and specificity as an MCL-1 inhibitor, the EC50 value of UMI-77 is 10 µmol/L [1]. In living cells, A-1210477 disrupted BIM/MCL-1 complexes. In MCL-1-dependent cancer cells, A-1210477 induced the hallmarks of mitochondrial apoptosis. In various malignant cell lines, A-1210477 induced apoptosis, synergizing with navitoclax. Data also demonstrate that A-1210477 acted through an on-target mechanism. It appeared as the first BH3 mimetic targeting MCL-1 [2].
The pharmacokinetics of A-1210477 are not favorable for in vivo use [5].
References: [1]. Lopez J, Bessou M, Riley JS, et al. Mito-priming as a method to engineer Bcl-2 addiction. Nature communications, 2016, 7:10538.[2]. Besbes S, Mirshahi M, Pocard M, et al. New dimension in therapeutic targeting of BCL-2 family proteins. Oncotarget, 2015, 6(15): 12862.[3]. Leverson JD, Zhang H, Chen J, et al. Potent and selective small-molecule MCL-1 inhibitors demonstrate on-target cancer cell killing activity as single agents and in combination with ABT-263 (navitoclax). Cell death & disease, 2015, 6(1): e1590.[4]. Mott JL, Kobayashi S, Bronk SF, et al. mir-29 regulates Mcl-1 protein expression and apoptosis. Oncogene, 2007, 26(42): 6133-6140.[5]. Opferman JT. Attacking cancer"s Achilles heel: antagonism of anti-apoptotic BCL-2 family members. FEBS Journal, 2015.
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磁珠如贴片磁珠，插件磁珠
他们都可能是同一种材质，非要区别那可能就是大小了 ，磁珠都非常的小，
电感多用于电源滤波回路，磁珠多用于信号回路，用于EMC对策磁珠主要用于抑制电磁辐射干扰，而电感用于这方面则侧重于抑制传导性干扰。两者都可用于处理EMC、EMI问题。磁珠是用来吸收超高频信号，象一些RF电路，PLL，振荡电路，含超高频存储器电路（DDR SDRAM，RAMBUS等）都需要在电源输入部分加磁珠，而电感是一种蓄能元件，用在LC振荡电路，中低频的滤波电路等，其应用频率范围很少超过错50MHZ。地的连接一般用电感，电源的连接也用电感，而对信号线则采用磁珠？
但实际上磁珠应该也能达到吸收高频干扰的目的啊？而且电感在高频谐振以后都不能再起电感的作用了,先必需明白EMI的两个途径，即：辐射和传导，不同的途径采用不同的抑制方法。前者用磁珠，后者用电感。对于扳子的IO部分，是不是基于EMC的目的可以用电感将IO部分和扳子的地进行隔离，比如将USB的地和扳子的地用10uH的电感隔离可以防止插拔的噪声干扰地平面？电感一般用于电路的匹配和信号质量的控制上。在模拟地和数字地结合的地方用磁珠。在模拟地和数字地结合的地方用磁珠。数字地和模拟地之间的磁珠用多大,磁珠的大小（确切的说应该是磁珠的特性曲线),取决于你需要磁珠吸收的干扰波的频率,为什么磁珠的单位和电阻是一样的呢？？都是欧姆！！磁珠就是阻高频嘛，对直流电阻低，对高频电阻高，不就好理解了吗， 比如1000R@100Mhz就是说对100M频率的信号有1000欧姆的电阻,因为磁珠的单位是按照它在某一频率产生的阻抗来标称的，阻抗的单位也是欧姆。磁珠的datasheet上一般会附有频率和阻抗的特性曲线图。一般以100MHz为标准，比如2012B601，就是指在100MHz的时候磁珠的Impedance为600欧姆。
电感多用于电源滤波回路，磁珠多用于信号回路，用于EMC对策磁珠主要用于抑制电磁辐射干扰，而电感用于这方面则侧重于抑制传导性干扰。两者都可用于处理EMC、EMI问题。磁珠是用来吸收超高频信号，象一些RF电路，PLL，振荡电路，含超高频存储器电路（DDR SDRAM，RAMBUS等）都需要在电源输入部分加磁珠，而电感是一种蓄能元件，用在LC振荡电路，中低频的滤波电路等，其应用频率范围很少超过错50MHZ。地的连接一般用电感，电源的连接也用电感，而对信号线则采用磁珠？
但实际上磁珠应该也能达到吸收高频干扰的目的啊？而且电感在高频谐振以后都不能再起电感的作用了,先必需明白EMI的两个途径，即：辐射和传导，不同的途径采用不同的抑制方法。前者用磁珠，后者用电感。对于扳子的IO部分，是不是基于EMC的目的可以用电感将IO部分和扳子的地进行隔离，比如将USB的地和扳子的地用10uH的电感隔离可以防止插拔的噪声干扰地平面？电感一般用于电路的匹配和信号质量的控制上。在模拟地和数字地结合的地方用磁珠。在模拟地和数字地结合的地方用磁珠。数字地和模拟地之间的磁珠用多大,磁珠的大小（确切的说应该是磁珠的特性曲线),取决于你需要磁珠吸收的干扰波的频率,为什么磁珠的单位和电阻是一样的呢？？都是欧姆！！磁珠就是阻高频嘛，对直流电阻低，对高频电阻高，不就好理解了吗， 比如1000R@100Mhz就是说对100M频率的信号有1000欧姆的电阻,因为磁珠的单位是按照它在某一频率产生的阻抗来标称的，阻抗的单位也是欧姆。磁珠的datasheet上一般会附有频率和阻抗的特性曲线图。一般以100MHz为标准，比如2012B601，就是指在100MHz的时候磁珠的Impedance为600欧姆。
