| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg |
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Purity: ≥98%
WEHI-539 hydrochloride, the HCl salt of WEHI-539, is a potent and selective inhibitor of BCL-XL with IC50 value of 1.1 nM. WEHI-539 increases the effects of carboplatin on caspase 3/7 activity, PARP cleavage, and annexin V labeling. In Ovcar-4 (5 μM in Ovcar-4) and Ovsaho (1 μM in Ovsaho) cells, WEHI-539 alone results in observable PARP cleavage. With IC50 and KD values near or below 1 nM and a slow dissociation rate, WEHI-539 not only binds to BCL-XL very tightly but also triggers apoptotic reactions that require BAX, BAK, or both. Additionally, its biological activity is linked to its binding profile because high levels of MCL-1, BCL-2, and BCL-W confer noticeable resistance. Additionally, its capacity to destroy platelets is a recognized indicator of on-target BCL-XL inhibition.
| Targets |
Bcl-xL (IC50 = 1.1 nM)
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| ln Vitro |
NSC 241240-induced caspase 3/7 activity, PARP cleavage, and annexin V labeling are enhanced by WEHI-539. In Ovcar-4 (5 μM in Ovcar-4) and Ovsaho (1 μM in Ovsaho) cells, WEHI-539 alone significantly increases PARP cleavage[2].
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| ln Vivo |
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| Enzyme 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.
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| Cell Assay |
Ovcar-8, Ovcar-3, Ovcar-4, and Ovsaho cells are grown in the RPMI medium, Igrov-1, Cov-362 and Cov-318 cells are grown in DMEM, and Fuov-1 cells are grown in a DMEM/F-12 nutrient solution. DMSO is used to prepare a 20 mM solution of ABT-737, ABT-199, and WEHI-539 (Medchem Express, NJ, USA). Cells are plated in 96-well plates for cell growth assays (5,000 cells/well for all cell lines, 2,500 cells/well for Ovcar-8). Cells receive drug therapy the following day. After 72 hours, the culture medium is taken out, the cells are fixed with 100 μL of cold 10% Trichloroacetic acid (TCA), incubated on ice for 30 minutes, and stained with 0.4% sulforhodamine B (SRB). The data are examined using the Graphpad Prism 4 program. A four-parameter Hill equation is fitted using non-linear regression. For drug combination studies, cells are exposed simultaneously to a range of NSC 241240 concentrations along with a fixed concentration of BH3 mimics, which is predicted from single agent studies to result in a 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. SRB staining is used to determine the number of living cells. It calculates a combination index (CI)[2].
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| Animal Protocol |
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| References |
| Molecular Formula |
C31H29N5O3S2
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| Molecular Weight |
620.18
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| Exact Mass |
619.15
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| Elemental Analysis |
C, 60.04; H, 4.88; Cl, 5.72; N, 11.29; O, 7.74; S, 10.34
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| CAS # |
2070018-33-4
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| Related CAS # |
WEHI-539;1431866-33-9
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| Appearance |
Solid powder
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| SMILES |
C1CC2=C(C=C(C=C2)C3=NC(=C(S3)CCCOC4=CC=C(C=C4)CN)C(=O)O)/C(=N/NC5=NC6=CC=CC=C6S5)/C1.Cl
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| InChi Key |
GJBYTVIQTMIXGA-DYICZVFTSA-N
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| InChi Code |
InChI=1S/C31H29N5O3S2.ClH/c32-18-19-10-14-22(15-11-19)39-16-4-9-27-28(30(37)38)34-29(40-27)21-13-12-20-5-3-7-24(23(20)17-21)35-36-31-33-25-6-1-2-8-26(25)41-31;/h1-2,6,8,10-15,17H,3-5,7,9,16,18,32H2,(H,33,36)(H,37,38);1H/b35-24+;
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| Chemical Name |
5-[3-[4-(aminomethyl)phenoxy]propyl]-2-[(8E)-8-(1,3-benzothiazol-2-ylhydrazinylidene)-6,7-dihydro-5H-naphthalen-2-yl]-1,3-thiazole-4-carboxylic acid;hydrochloride
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.03 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.03 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6124 mL | 8.0622 mL | 16.1244 mL | |
| 5 mM | 0.3225 mL | 1.6124 mL | 3.2249 mL | |
| 10 mM | 0.1612 mL | 0.8062 mL | 1.6124 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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