| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
ATM 6.3 nM (IC50) DNA-PKcs 1.7 μM (IC50)
ATM kinase (ataxia-telangiectasia mutated). KU-60019 is a potent and selective inhibitor of ATM kinase. |
|---|---|
| ln Vitro |
KU-60019 is KU-55933's enhanced counterpart. KU-55933 is highly selective for ATM kinase, with an in vitro IC50 of 13 nM and a Ki of 2.2 nM, utilizing a panel of 60 protein kinases. An enhanced ATM kinase inhibitor, KU-60019 has an IC50 of 6.3 nM, which is roughly half that of KU-55933. DNA-PKcs and ATR had IC50 values of 1.7 and >10 μM, respectively, over 270 and 1600 times greater than ATM. When it comes to preventing radiation-induced phosphorylation of important ATM targets in human glioma cells, KU-60019 is ten times more efficient than KU-55933. When exposed to 10 μM of KU-55933, human U87 glioma cells showed complete inhibition of p53 (S15) phosphorylation, but not at 3 μM. In contrast, 1 hour after irradiation, γ-H2AX levels were only slightly reduced. On the other hand, at 3 μM and 1 μM, respectively, KU-60019 completely and partially blocked p53 phosphorylation [1].
KU-60019 is a potent ATM kinase inhibitor with an IC50 of 6.3 nM. It is a reversible inhibitor that blocks the phosphorylation of ATM substrate proteins. KU-60019 is highly selective for ATM over other kinases, with minimal off-target effects against a panel of 229 protein kinases. The compound sensitizes glioma cells to radiation and inhibits the migration and invasion of glioma cells in vitro. |
| ln Vivo |
PTEN-deficient control tumors grew four times larger than PTEN wild-type controls, however when treated with KU-60019, PTEN-deficient tumor development slowed statistically significantly. This reduction of growth was most noticeable during the first few days of the experiment (days 5–12) and following the administration of KU–60019 (days 1–5) [2].
In vivo, KU-60019 has been shown to sensitize glioma cells to radiation. As an ATM kinase inhibitor, it disrupts the DNA damage response and may enhance the efficacy of DNA-damaging therapies. |
| Enzyme Assay |
In vitro kinase assays for KU-60019 are performed to evaluate its inhibitory activity against ATM kinase. The kinase is incubated with peptide substrates and ATP in the presence of varying concentrations of KU-60019. The inhibition of kinase activity is measured by assessing the phosphorylation of the substrate, and IC50 values are calculated from the concentration-response curves. Selectivity profiling is performed against a panel of kinases to confirm its specificity.
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| Cell Assay |
In vitro cell-based assays are conducted to evaluate the effects of KU-60019 on ATM signaling and cell viability. Cells are treated with KU-60019, and ATM phosphorylation and the phosphorylation of downstream targets such as CHK2, p53, and H2AX are measured by Western blotting. The compound's ability to sensitize cells to radiation is evaluated by measuring cell viability and clonogenic survival following irradiation. Cell migration and invasion are assessed using transwell or scratch assays.
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| Animal Protocol |
In vivo animal studies with KU-60019 are conducted in rodent models, such as glioma xenograft models, to evaluate its antitumor efficacy and radiosensitizing effects. The compound is typically administered via oral or intraperitoneal routes. Its effects on tumor growth, survival, and biomarkers of ATM signaling are assessed in combination with radiation.
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| ADME/Pharmacokinetics |
No detailed pharmacokinetic data are publicly available for KU-60019. As a small molecule inhibitor, its ADME properties would be characterized in standard preclinical studies.
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| Toxicity/Toxicokinetics |
No specific toxicity data are publicly available for KU-60019. As an ATM kinase inhibitor, its toxicity profile would be expected to be related to its mechanism of action. Standard safety assessments would be required for any therapeutic development.
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| References |
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| Additional Infomation |
KU-60019 is a potent and selective ATM kinase inhibitor with an IC50 of 6.3 nM. It sensitizes glioma cells to radiation and inhibits cell migration and invasion. KU-60019 is a valuable research tool for studying the role of ATM in DNA damage responses and cancer biology. The compound is not approved for human therapeutic use and is strictly for research purposes.
|
| Molecular Formula |
C30H33N3O5S
|
|---|---|
| Molecular Weight |
547.67
|
| Exact Mass |
547.214
|
| CAS # |
925701-46-8
|
| PubChem CID |
15953870
|
| Appearance |
Light yellow to khaki solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
786.6±60.0 °C at 760 mmHg
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| Flash Point |
429.5±32.9 °C
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| Vapour Pressure |
0.0±2.7 mmHg at 25°C
|
| Index of Refraction |
1.645
|
| LogP |
5.9
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
39
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| Complexity |
972
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| Defined Atom Stereocenter Count |
2
|
| SMILES |
C[C@@H]1CN(C[C@@H](O1)C)CC(=O)NC2=CC3=C(C=C2)SC4=C(C3)C=CC=C4C5=CC(=O)C=C(O5)N6CCOCC6
|
| InChi Key |
SCELLOWTHJGVIC-BGYRXZFFSA-N
|
| InChi Code |
InChI=1S/C30H33N3O5S/c1-19-16-32(17-20(2)37-19)18-28(35)31-23-6-7-27-22(13-23)12-21-4-3-5-25(30(21)39-27)26-14-24(34)15-29(38-26)33-8-10-36-11-9-33/h3-7,13-15,19-20H,8-12,16-18H2,1-2H3,(H,31,35)/t19-,20+
|
| Chemical Name |
2-[(2S,6R)-2,6-dimethylmorpholin-4-yl]-N-[5-(6-morpholin-4-yl-4-oxopyran-2-yl)-9H-thioxanthen-2-yl]acetamide
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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: 100 mg/mL (182.59 mM)
Ethanol: 10 mg/mL (18.26 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.56 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 (4.56 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 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 | 1.8259 mL | 9.1296 mL | 18.2592 mL | |
| 5 mM | 0.3652 mL | 1.8259 mL | 3.6518 mL | |
| 10 mM | 0.1826 mL | 0.9130 mL | 1.8259 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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