embalaje : 1mLx10mM(inDMSO)
Teléfono : +1 850 650 7790
Synonyms: A1155463, A 1155463
| Description | A-1155463, a highly potent and selective BCL-XL inhibitor, shows picomolar binding affinity to BCL-XL, and >1000-fold weaker binding to BCL-2 and related proteins BCL-W(Ki=19 nM) and MCL-1(Ki>440 nM). |
| Targets & IC50 | BCL-XL:<0.01 nM(Ki), Bcl-2:80 nM (Ki) |
| In vitro | A-1155463 disrupts BCL-XL-BIM but not BCL-2-BIM complexes in cells. A-1155463 kills BCL-XL-dependent Molt-4 cells (EC50=70 nM) but has no measurable cytotoxicity against BCL-2-dependent RS4;11 cells (EC50>5 mM). A-1155463 induces the hallmarks of apoptosis, as evidenced by the release of cytochrome c from mitochondria, caspase activation, and the accumulation of caspase-dependent sub-G0-G1 DNA content in BCL-XL-dependent H146 cells[2]. |
| In vivo | Following a single 5 mg/kg IP dose of A-1155463 in nontumor bearing SCID-Beige mice, platelet counts fall dramatically as measured at 6 h postdose and then rebound to normal levels within 72 h. Daily Dosing at 5 mg/kg IP to SCID-Beige mice that had been inoculated with BCL-XL-dependent H146 tumor cells for 14 days causes a statistically significant inhibition of tumor growth (maximum tumor growth inhibition = 44%), which is alleviated upon cessation of dosing[1]. |
| Synonyms | A1155463, A 1155463 |
| Kinase Assay | Recombinant p38 isoforms are activated by Mkk6(E) under the following conditions: p38 (100 ng/mL), Mkk6(E) (30 ng/mL), ATP (100 mM) are mixed in kinase buffer (25 mM Hepes, 25 mM b-glycerophosphate, 0.1 mM sodium orthovanadate, 25 mM MgCl2, 2.5 mM DTT, pH 7.4) and incubated for 30 min at 30°C. A typical assay reaction for Mnk1 activity contained Mnk1 (2 ng/mL), HA-eIF4E (10 ng/mL), ATP (300 mM) in kinase buffer. The reaction is started by addition of activated p38 (0.03-3 ng/mL) and stopped after 30 min at 30°C by addition of SDS loading buffer. Inhibitors of Mnk1 are identified under the same assay conditions, except that Mnk1 is pre-activated using active p38a before exposure to the substrate and inhibitors. |
| Cell Research | Cells are treated with increasing concentration of A-1155463. Cells are assayed for viability after 72 h using the CellTiter-Glo luminescent cell viability assay according to the manufacturer's protocol. Results are normalized to cells without treatment. EC50 is calculated using the GraphPad Prism software.(Only for Reference) |
| Animal Research | Animal Models: SCID-Beige MiceFormulation: 5% DMSO, 10% EtOH, 20% Cremaphor ELP, and 65% D5WDosages: 5 mg/kgAdministration: i.p. |
| Molecular Weight | 669.79 |
| Formula | C35H32FN5O4S2 |
| Cas No. | 1235034-55-5 |
| Smiles | C(NC1=NC=2C(S1)=CC=CC2)(=O)C3=C4C(CCN(C4)C5=NC(C(O)=O)=C(CCCOC6=C(F)C=C(C#CCN(C)C)C=C6)S5)=CC=C3 |
| Relative Density. | 1.45 g/cm3 (Predicted) |
| Storage | Keep away from moisture Powder: -20°C for 3 years | In solvent: -80°C for 1 year Shipping with blue ice/Shipping at ambient temperature. | |||||||||||||||||||||||||||||||||||
| Solubility Information | DMSO: 100 mg/mL (149.3 mM), Sonication is recommended. H2O: < 1 mg/mL (insoluble or slightly soluble) Ethanol: 100 mg/mL (149.3 mM), Sonication is recommended. | |||||||||||||||||||||||||||||||||||
| In Vivo Formulation | 10% DMSO+40% PEG300+5% Tween 80+45% Saline: 4 mg/mL (5.97 mM), Sonication is recommended. Please add the solvents sequentially, clarifying the solution as much as possible before adding the next one. Dissolve by heating and/or sonication if necessary. Working solution is recommended to be prepared and used immediately. The formulation provided above is for reference purposes only. In vivo formulations may vary and should be modified based on specific experimental conditions. | |||||||||||||||||||||||||||||||||||
Solution Preparation Table | ||||||||||||||||||||||||||||||||||||
DMSO/Ethanol
Note : The dilution table applies only to solid products. For liquid products, please calculate the stock solution based on the stated concentration and/or density. | ||||||||||||||||||||||||||||||||||||
For example, if the intended dosage is 10 mg/kg for animals weighing 20 g , with a dosing volume of 100 μL per animal, and a total of 10 animals are to be administered, using a formulation of 
10% DMSO+ 40% PEG300+ 5% Tween 80+ 45% Saline/PBS/ddH2O , the resulting working solution concentration would be 2 mg/mL.Dissolve 2 mg of the compound in 100 μL DMSO to obtain a stock solution at a concentration of 20 mg/mL . If the required concentration exceeds the compound's known solubility, please contact us for technical support before proceeding.
1) Add 100 μL of the DMSO stock solution to 400 µL PEG300 and mix thoroughly until the solution becomes clear.
2) Add 50 µL Tween 80 and mix well until fully clarified.
3) Add 450 µL Saline,PBS or ddH2O and mix thoroughly until a homogeneous solution is obtained.
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