| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
DNA-PK-IN-11 targets DNA-dependent protein kinase (DNA-PK), a critical enzyme involved in the non-homologous end joining (NHEJ) pathway of DNA double-strand break repair. DNA-PK is a serine/threonine protein kinase that plays a central role in the cellular response to DNA damage. Inhibition of DNA-PK sensitizes cancer cells to DNA-damaging agents such as ionizing radiation and chemotherapeutic drugs that induce double-strand breaks.
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| ln Vitro |
In vitro studies demonstrate that DNA-PK-IN-11 potently inhibits DNA-PK enzymatic activity with an IC50 of <0.1 μM. This inhibition disrupts the NHEJ repair pathway, leading to the accumulation of unrepaired DNA double-strand breaks. In cancer cell lines, DNA-PK-IN-11 enhances the cytotoxicity of radiation and DNA-damaging chemotherapeutic agents by preventing repair of the induced DNA damage. The compound shows potential for overcoming resistance mechanisms associated with enhanced DNA repair capacity.
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| ln Vivo |
In vivo efficacy of DNA-PK-IN-11 has been evaluated in preclinical tumor models, where it enhances the anti-tumor activity of radiation therapy and chemotherapy. By inhibiting DNA-PK in the tumor, the compound prevents DNA repair in cancer cells, leading to increased cell death and tumor regression. The compound's ability to sensitize tumors to conventional therapies makes it a promising candidate for combination therapy approaches in oncology research.
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| Enzyme Assay |
Non-cellular enzyme assays for DNA-PK-IN-11 typically involve measuring DNA-PK kinase activity using purified enzyme and a peptide substrate. The assay is performed in the presence of varying concentrations of the test compound to determine the IC50 value. DNA-PK activity is measured by incorporating 32P-ATP into a DNA-PK-specific peptide substrate, and the phosphorylated product is quantified by scintillation counting or phosphorimaging. Data are analyzed to calculate the concentration required for 50% inhibition.
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| Cell Assay |
In vitro cellular experiments with DNA-PK-IN-11 are conducted in cancer cell lines to assess its effects on DNA repair and cell viability. Cells are treated with the compound, often in combination with ionizing radiation or chemotherapeutic agents. DNA damage is assessed using markers such as γ-H2AX foci formation, and cell survival is measured using clonogenic assays or MTT assays. The compound's ability to radiosensitize or chemosensitize cells is quantified by comparing survival fractions between treated and untreated groups.
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| Animal Protocol |
In vivo animal studies for DNA-PK-IN-11 are performed in murine xenograft models of human cancers. Tumor-bearing mice are treated with the compound, typically via oral or intraperitoneal administration, alone or in combination with radiation or chemotherapy. Tumor growth is monitored over time, and endpoints include tumor volume measurements, tumor growth delay, and survival analysis. Pharmacodynamic markers of DNA damage and repair inhibition are evaluated in tumor tissues.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of DNA-PK-IN-11 include a molecular weight of 428.42 and a molecular formula of C23H17FN6O2. The compound has a LogP of 2.5 and a tPSA of 87.3. It is stable as a powder at -20°C for 3 years and in solution at -80°C for 6 months. The compound is soluble in DMSO at approximately 5 mg/mL. For in vivo use, formulations may include DMSO, Tween 80, and saline.
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| Toxicity/Toxicokinetics |
Standard toxicity assessments for DNA-PK-IN-11 would include acute and sub-chronic toxicity studies in rodents to determine safety margins and identify potential target organs. As a DNA repair inhibitor, the compound may affect rapidly dividing normal tissues such as bone marrow and intestinal epithelium. Comprehensive toxicology data are typically generated during preclinical development. Researchers should consult the safety data sheet and handle the compound with appropriate laboratory safety precautions.
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| References | |
| Additional Infomation |
DNA-PK-IN-11 is identified by the chemical name 3-fluoro-4-(7-methoxy-3-methyl-8-(1-methyl-1H-pyrazol-4-yl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]quinolin-1-yl)benzonitrile. The CAS number is 1360628-91-6 and the PubChem CID is 56847587. Purity is typically ≥98%. The compound is for research use only. It is classified as a DNA damage-related compound.
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| Molecular Formula |
C23H17FN6O2
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|---|---|
| Molecular Weight |
428.41848731041
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| Exact Mass |
428.139
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| CAS # |
1360628-91-6
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| PubChem CID |
56847587
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
2.5
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
32
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| Complexity |
775
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CN1C=C(C=N1)C2=C(C=C3C(=C2)C4=C(C=N3)N(C(=O)N4C5=C(C=C(C=C5)C#N)F)C)OC
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| InChi Key |
OOCGUVCGJIUQKC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H17FN6O2/c1-28-12-14(10-27-28)15-7-16-18(8-21(15)32-3)26-11-20-22(16)30(23(31)29(20)2)19-5-4-13(9-25)6-17(19)24/h4-8,10-12H,1-3H3
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| Chemical Name |
3-fluoro-4-[7-methoxy-3-methyl-8-(1-methylpyrazol-4-yl)-2-oxoimidazo[4,5-c]quinolin-1-yl]benzonitrile
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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 :~5 mg/mL (~11.67 mM; with sonication (<60°C))
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3342 mL | 11.6708 mL | 23.3416 mL | |
| 5 mM | 0.4668 mL | 2.3342 mL | 4.6683 mL | |
| 10 mM | 0.2334 mL | 1.1671 mL | 2.3342 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.
Link: https://clinicaltrials.gov/ct2/show/NCT03225105
Conditions:Solid TumorsProducts are for research use only; We do not sell to patients
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