产品属性：
产品名称 | 规格 | CAS号 | 型号 |
A-1210477 | 5 mg 10 mg 25 mg 50 mg 100 mg | 1668553-26-1 | EY-Y0165150 |
Cas No.1668553-26-1
别名 N/A
化学名 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
分子式 C46H55N7O7S
分子量 850.04
溶解度 <1.7mg/mL in DMSO
储存条件 Store at -20°C
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.
Shipping Condition Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request
产品描述：
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.
关键字： 1668553-26-1;C46H55N7O7S;A-1210477;
上海一研生物科技有限公司Shanghai yiyan bio-technology Co. Ltd.主要从事免疫学、分子生物学和常规生化试剂等为一体的科研产品销售企业，公司自成立以来，秉承""全心全意服务于科研工作者""的企业理念，立足生物科技领域，运用生物技术和科研试剂，发展现代生物科技，为各类大中小医院及其它医疗机构、高等院校、科研院所、企事业单位提供优质的产品，服务生物科技领域的科学研究人员。
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