KU-0060648
KU-0060648 (CAS: 881375-00-4) is a small-molecule inhibitor that targets DNA-dependent protein kinase (DNA-PK) and phosphoinositide 3-kinase (PI-3K). It suppresses DNA-PK autophosphorylation with IC50 values of 0.17 μM in SW620 colon cancer cells and 0.019 μM in MCF7 breast cancer cells, and inhibits PI-3K–mediated AKT phosphorylation in MCF7 cells at 0.039 μM. In vitro, KU-0060648 reduces cell proliferation, particularly in DNA-PKcs–proficient cell lines, and enhances cytotoxicity of chemotherapeutic agents such as etoposide and doxorubicin. In vivo, it delays tumor growth and potentiates chemotherapy-induced tumor regression in xenograft models without increasing unacceptable toxicity. KU-0060648 is in preclinical development as a tool to study DNA damage repair and chemosensitization.
References:
[1] Munck JM, Batey MA, Zhao Y, Jenkins H, Richardson CJ, Cano C, Tavecchio M, Barbeau J, Bardos J, Cornell L, Griffin RJ, Menear K, Slade A, Thommes P, Martin NM, Newell DR, Smith GC, Curtin NJ. Chemosensitization of cancer cells by KU-0060648, a dual inhibitor of DNA-PK and PI-3K. Mol Cancer Ther. 2012;11(8):1789-98.
| Storage | Store at -20°C |
| M.Wt | 582.71 |
| Cas No. | 881375-00-4 |
| Formula | C33H34N4O4S |
| Solubility | Limited solubility, soluble in HCl |
| Chemical Name | 2-(4-ethylpiperazin-1-yl)-N-[4-(2-morpholin-4-yl-4-oxochromen-8-yl)dibenzothiophen-1-yl]acetamide |
| SDF | Download SDF |
| Canonical SMILES | CCN1CCN(CC1)CC(=O)NC2=C3C4=CC=CC=C4SC3=C(C=C2)C5=CC=CC6=C5OC(=CC6=O)N7CCOCC7 |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1]: | |
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Cell lines |
Human breast cancer cells (MCF7, T47D and MDA-MB-231) and colon cancer cells (LoVo and SW620) |
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Preparation method |
The solubility of this compound in DMSO is limited. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
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Reacting condition |
1 μM; 5 days |
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Applications |
Five-day exposure to 1 μM KU-0060648 resulted in more than 50% inhibition of cell growth in all cancer cell lines. KU-0060648 showed the greatest effect on growth inhibition of LoVo and MCF7 cells, the total cell growth of which over 5 days was only 10% and 4% of that of the control group, respectively. |
| Animal experiment [1]: | |
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Animal models |
Mice bearing MCF7 xenografts |
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Dosage form |
10 mg/kg; i.p.; b.i.d. |
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Applications |
In mice bearing MCF7 xenografts, KU-0060648 alone resulted in a median growth delay of 30 days with negligible toxicity, and the combination of KU-0060648 and Etoposide Phosphate caused a median growth delay of 55 days with acceptable toxicity. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Munck JM, Batey MA, Zhao Y, Jenkins H, Richardson CJ, Cano C, Tavecchio M, Barbeau J, Bardos J, Cornell L, Griffin RJ, Menear K, Slade A, Thommes P, Martin NM, Newell DR, Smith GC, Curtin NJ. Chemosensitization of cancer cells by KU-0060648, a dual inhibitor of DNA-PK and PI-3K. Mol Cancer Ther. 2012;11(8):1789-98. |
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| Description | KU-0060648 is a dual, ATP-competitive inhibitor of DNA-dependent protein kinase (DNA-PK) and PI3-K with IC50 values of 19 nM, <0.1 nM, 0.5nM and 4 nM for DNA-PK, PI3-Kδ, PI3-Kβ and PI3-Kα, respectively. | |||||
| Targets | DNA-PK | PI3-Kδ | PI3-Kβ | PI3-Kα | ||
| IC50 | 19 nM | <0.1 nM | 0.5nM | 4 nM | ||
Quality Control & MSDS
- View current batch:
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Purity = 98.00%
- COA (Certificate Of Analysis)
- MSDS (Material Safety Data Sheet)
- Datasheet
Chemical structure
Related Biological Data
