A-1210477 |
Catalog No.GC16278 |
MCL-1 inhibitor
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1668553-26-1
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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. |
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.
Cas No. | 1668553-26-1 | SDF | |
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/mL in DMSO | Storage | Store at -20°C |
General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. |
Prepare stock solution | |||
1 mg | 5 mg | 10 mg | |
1 mM | 1.1764 mL | 5.8821 mL | 11.7642 mL |
5 mM | 0.2353 mL | 1.1764 mL | 2.3528 mL |
10 mM | 0.1176 mL | 0.5882 mL | 1.1764 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Average Rating: 5
(Based on Reviews and 17 reference(s) in Google Scholar.)GLPBIO products are for RESEARCH USE ONLY. Please make sure your review or question is research based.
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