CAS NO: | 2070018-33-4 |
规格: | ≥98% |
包装 | 价格(元) |
5mg | 电议 |
10mg | 电议 |
25mg | 电议 |
50mg | 电议 |
100mg | 电议 |
250mg | 电议 |
500mg | 电议 |
Molecular Weight (MW) | 620.18 |
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Formula | C31H29N5O3S2.HCl |
CAS No. | 2070018-33-4 (HCl salt); |
Storage | -20℃ for 3 years in powder form |
-80℃ for 2 years in solvent | |
Solubility (In vitro) | DMSO: 100 mg/mL (161.2 mM) |
Water: N/A | |
Ethanol: N/A | |
SMILES Code | O=C(C1=C(CCCOC2=CC=C(CN)C=C2)SC(C(C=C/34)=CC=C4CCCC3=N/NC5=NC6=CC=CC=C6S5)=N1)O.[H]Cl |
Synonyms | WEHI539 hydrochloride; WEHI-539; WEHI 539 HCl |
In Vitro | In vitro activity: WEHI-539 hydrochloride is a selective inhibitor of Bcl-XL, it augments carboplatin induced caspase 3/7 activity, PARP cleavage and annexin V labelling. As a single agent, WEHI-539 causes noticeable PARP cleavage in Ovcar-4 (5 μM in Ovcar-4.) and Ovsaho (1 μM in Ovsaho) cells. Kinase Assay: The assay buffer (stock 50 mM HEPES and 100 mM NaCl, pH 7.5) is prepared fresh daily and adjusted to 5 mM DTT, casein (0.1 mg/mL sodium salt; aliquots stored at -20 °C) and Tween 20. Cell Assay: WEHI-539 is dissolved in DMSO (20 mM) and stored, and then diluted with appropriate media before use. Ovcar-8, Ovcar-3, Ovcar-4 and Ovsaho cells are grown in the RPMI, Igrov-1, Cov-362 and Cov-318 cells are grown in DMEM and Fuov-1 cells are grown in DMEM/F-12 nutrient mixture. ABT-737, ABT-199 and WEHI-539, are prepared as a 20 mM solution in DMSO. For cell growth assays, cells are plated in 96 wells plate (5,000 cells/well for all cell lines except Ovcar-8 which is plated at a density of 2,500 cells/well). The next day, cells are treated with drugs. After 72 h the culture medium is removed and the cells are fixed with 100 μL of cold 10 % Trichloroacetic acid (TCA), incubated on ice for 30 min and stained with 0.4 % sulforhodamine B (SRB). The data are analysed by using Graphpad Prism 4 software. Non-linear regression is used to fit a four parameters Hill equation. For drug combinations studies the cells are exposed simultaneously to a range of concentrations of carboplatin combined with fixed concentration of BH3 mimetics that is expected from the single agent studies to cause 5 % growth inhibition: ABT-737, 1 μM in Ovcar-8, Ovcar-3 and Igrov-1, 2 μM in Ovcar-4 and Ovsaho and 6 μM in Cov-362; ABT-199, 1 μM in Ovcar-4, 2 μM in Ovcar-3, Igrov-1, Cov-362 and Ovsaho and 3 μM in Ovcar-8; WEHI-539, 0.2 μM in Igrov-1, 0.3 μM in Ovcar-8, 1 μM in Ovcar-3 and Ovsaho, 3.1 μM in Cov-362 and 5 μM in Ovcar-4. Surviving cell number is assessed by SRB staining. A combination index (CI) is calculated. |
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In Vivo | |
Animal model | |
Formulation & Dosage | |
References | Nat Chem Biol. 2013 Jun;9(6):390-7; J Ovarian Res. 2016 Apr 14;9:25. |