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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%
KU0060648 (KU-0060648) is a novel, potent and selective inhibitor of DNA-dependent protein kinase (DNA-PK) with anticancer activity. It inhibits DNA-PK with an IC50 of 8.6 nM and exhibits 20-1000 fold selectivity for DNA-PK over other PIKKs and a panel of 60 kinases. KU-0060648 is also regarded as a DNA-PK and PI-3K dual inhibitor. With IC(50) values of 0.019 mol/L (MCF7 cells) and 0.17 mol/L (SW620 cells), KU-0060648 inhibited cellular DNA-PK autophosphorylation, and with IC(50) values of 0.039 mol/L (MCF7 cells) and more than 10 mol/L (SW620 cells), it inhibited PI-3K-mediated AKT phosphorylation. Hepatocellular carcinoma cells are inhibited by KU-0060648 through both DNA-PKcs-dependent and -independent mechanisms.
Targets |
PI3Kα (IC50 = 4 nM); PI3Kβ (IC50 = 0.5 nM); PI3Kγ (IC50 = 0.594 μM);PI3Kδ (IC50 = 0.1 nM); DNA-PK (IC50 = 8.6 nM)
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ln Vitro |
KU-0060648 exhibits differential effects on growth inhibition, but is not profoundly cytotoxic in a panel of human cancer cell lines. When compared to SW620 cells, MCF7 cells exhibit more potent inhibition of DNA-PK and PI-3K. In MCF7 cells, exposure to 1 mM KU-0060648 for five days significantly reduces cell proliferation by more than 95%, but only by 55% in SW620 cells. In clonogenic survival assays, KU-0060648 increases etoposide and doxorubicin's cytotoxicity across a panel of DNA-PKcs-proficient cells, but not in DNA-PKcs-deficient cells, demonstrating that the increased cytotoxicity of the topoisomerase II poisons is caused by DNA-PK inhibition. [1]
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ln Vivo |
KU-0060648 increases the anti-tumour activity of etoposide in both MCF7 and SW620 xenograft models, and has single-agent activity in the MCF7 xenograft model. [1]
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Cell Assay |
SRB assay
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Animal Protocol |
human-tumor SW620 or MCF7 xenograft models
10 mg/kg, twice daily i.p. |
References |
Molecular Formula |
C33H34N4O4S
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Molecular Weight |
582.7125
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Exact Mass |
582.23
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Elemental Analysis |
C, 68.02; H, 5.88; N, 9.61; O, 10.98; S, 5.50
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CAS # |
881375-00-4
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Related CAS # |
881375-00-4
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Appearance |
Solid powder
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SMILES |
CCN1CCN(CC1)CC(=O)NC2=C3C4=CC=CC=C4SC3=C(C=C2)C5=CC=CC6=C5OC(=CC6=O)N7CCOCC7
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InChi Key |
AATCBLYHOUOCTO-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C33H34N4O4S/c1-2-35-12-14-36(15-13-35)21-29(39)34-26-11-10-23(33-31(26)25-6-3-4-9-28(25)42-33)22-7-5-8-24-27(38)20-30(41-32(22)24)37-16-18-40-19-17-37/h3-11,20H,2,12-19,21H2,1H3,(H,34,39)
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Chemical Name |
2-(4-ethylpiperazin-1-yl)-N-[4-(2-morpholin-4-yl-4-oxochromen-8-yl)dibenzothiophen-1-yl]acetamide
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Synonyms |
KU0060648; KU 0060648; KU-0060648
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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 |
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) |
DMSO: 2~2.8 mg/mL (3.4~4.8 mM)
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.28 mg/mL (0.48 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 2.8 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: ≥ 0.28 mg/mL (0.48 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), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 2.8 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. View More
Solubility in Formulation 3: ≥ 0.28 mg/mL (0.48 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 30% propylene glycol, 5% Tween 80, 65% D5W: 20 mg/mL |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 1.7161 mL | 8.5806 mL | 17.1612 mL | |
5 mM | 0.3432 mL | 1.7161 mL | 3.4322 mL | |
10 mM | 0.1716 mL | 0.8581 mL | 1.7161 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.