KU-0060648 |
| رقم الكتالوجGC14346 |
KU-0060648 هو مثبط مزدوج لـ PI3K و DNA-PK مع IC50s من 4 نانومتر و 0.5 نانومتر و 0.1 نانومتر و 0.594 نانومتر و 8.6 نانومتر لـ PI3Kα و PI3Kβ و PI3Kγ و PI3Kδ و DNA-PK ، على التوالي
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 881375-00-4
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
IC50: KU-0060648 inhibited cellular DNA-PK autophosphorylation with IC50 values of 0.17 μmol/L (SW620 cells) and 0.019 μmol/L (MCF7 cells), and PI-3K–mediated AKT phosphorylation with IC50 values of 0.039 μmol/L (MCF7 cells) and more than 10 μmol/L (SW620 cells).
DNA double-strand breaks (DSB) are the most cytotoxic lesions induced by topoisomerase II poisons. Nonhomologous end joining (NHEJ) is a major pathway for DSB repair and requires DNA-dependent protein kinase (DNA-PK) activity. DNA-PK catalytic subunit (DNA-PKcs), which promotes cell survival and proliferation and is upregulated in many cancers, is structurally similar to PI-3K,. KU-0060648 is a dual inhibitor of DNA-PKand PI-3K in vitro.
In vitro: KU-0060648 was investigated in a panel ofhumanbreast and colon cancer cells. Five-day exposure to 1 μM KU-0060648 was found to inhibite cell proliferation by more than 95% in MCF7 cells but only by 55% in SW620 cells. KU-0060648 increased the etoposide and doxorubicin cytotoxicity across the DNA-PKcs–proficient cell panel rather than in DNA-PKcs–deficient cells, therefore confirming the enhanced cytotoxicity was due to the inhibition of DNA-PK [1].
In vivo: In mice bearing SW620 and MCF7 xenografts, KU-0060648 concentrations that were sufficient for in vitro growth inhibition and chemosensitization were maintained within the tumor at nontoxic doses for at least 4 hours. KU-0060648 alone delayed the MCF7 xenografts growth and increased etoposide-induced tumor growth delay in both in MCF7 and SW620 xenografts by up to 4.5 folds, without causing etoposide toxicity to unacceptable levels [1].
Clinical trial: KU-0060648 is still in pre-clinical development stage and no clinicl trial is ongoing currently.
Reference:
[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.
| Cell experiment [1]: | |
|
Cell lines |
Human breast cancer cells (MCF7, T47D and MDA-MB-231) and colon cancer cells (LoVo and SW620) |
|
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. |
|
Reacting condition |
1 μM; 5 days |
|
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]: | |
|
Animal models |
Mice bearing MCF7 xenografts |
|
Dosage form |
10 mg/kg; i.p.; b.i.d. |
|
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. |
|
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. |
|
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. | |
| Cas No. | 881375-00-4 | SDF | |
| Chemical Name | 2-(4-ethylpiperazin-1-yl)-N-[4-(2-morpholin-4-yl-4-oxochromen-8-yl)dibenzothiophen-1-yl]acetamide | ||
| Canonical SMILES | CCN1CCN(CC1)CC(=O)NC2=C3C4=CC=CC=C4SC3=C(C=C2)C5=CC=CC6=C5OC(=CC6=O)N7CCOCC7 | ||
| Formula | C33H34N4O4S | M.Wt | 582.71 |
| الذوبان | DMF: 1 mg/ml,DMSO: 1 mg/ml | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
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 |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 21 reference(s) in Google Scholar.)
GLPBIO products are for RESEARCH USE ONLY. Please make sure your review or question is research based.
Required fields are marked with *