TDP1-IN-5
TDP1-IN-5 is a tyrosyl-DNA phosphodiesterase 1 (TDP1) inhibitor with an IC50 of 2.2 μM. By targeting TDP1 both intracellularly and extracellularly, TDP1-IN-5 inhibits the NHEJ repair pathway, arrests the cell cycle at the G2/M phase, upregulates PIG3 to enhance ROS, and ultimately significantly potentiates ionizing radiation (IR)-induced DNA damage and apoptosis. TDP1-IN-5 can be used in the research of colorectal cancer.
For research use only. We do not sell to patients.
- CAS No.: 3115524-78-9
- Formula: C34H45N5O5
- Molecular Weight:603.75
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
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Biological Activity
TDP1-IN-5 (Compound A6) (0.025-0.1 μM) exhibits strong radiosensitizing activity in HCT116 cells, with 83% cell killing when combined with 2 GY IR at 0.1 μM, and shows synergistic activity with a CI value as low as 0.20[1].
TDP1-IN-5 (Compound A6) (5-25 μM; 1 h) targets cellular TDP1 in HCT116 cells, stabilizing TDP1-DNA covalent complexes in a dose-dependent manner, with enhanced stabilization when combined with ionizing radiation[1].
TDP1-IN-5 (Compound A6) (1.25-5.0 μM) suppresses NHEJ repair activity in HCT116 cells in vitro in a dose-dependent manner, reducing repair by up to 42% at 5.0 μM[1].
TDP1-IN-5 (Compound A6) (5 μM; 6 h) enhances ionizing radiation-induced DNA damage in HCT116 cells, increasing γH2AX foci to 4.2-fold when combined with 4 GY IR at 5 μM[1].
TDP1-IN-5 (Compound A6) (1.25-2.5 μM) upregulates PIG3 protein expression in HCT116 cells, both alone and in combination with 4 GY ionizing radiation[1].
TDP1-IN-5 (Compound A6) (10 μM) enhances ionizing radiation-induced ROS production in HCT116 cells at 10 μM, while not inducing ROS production on its own[1].
TDP1-IN-5 (Compound A6) (5-10 μM; 24 h) induces G2/M cell cycle arrest in HCT116 cells in a dose-dependent manner, with enhanced arrest when combined with 4 GY ionizing radiation[1].
TDP1-IN-5 (Compound A6) (5-10 μM; 24 h) induces apoptosis in HCT116 cells in a dose-dependent manner, and significantly enhances ionizing radiation-induced apoptosis, reaching a 43.8% apoptotic ratio when combined with 4 GY IR at 10 μM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HCT116 human colorectal cancer cells
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Concentration:5 μM
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Incubation Time:6 h
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Result:Increased γH2AX foci by 1.5-fold when used alone compared to untreated cells.
Increased γH2AX foci to 4.2-fold above untreated levels when combined with 4 GY ionizing radiation (IR).
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Cell Line:HCT116 human colorectal cancer cells
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Concentration:5 μM, 10 μM
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Incubation Time:24 h
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Result:Increased the G2/M phase cell proportion from 27.9% (control) to 40.2% at 5 μM when used alone.
Increased the G2/M phase cell proportion from 27.9% (control) to 47.9% at 10 μM when used alone.
Increased the G2/M phase proportion from 40.4% (IR alone) to 53.1% at 5 μM when combined with 4 GY ionizing radiation (IR).
Increased the G2/M phase proportion from 40.4% (IR alone) to 59.0% at 10 μM when combined with 4 GY IR.
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Cell Line:HCT116 human colorectal cancer cells
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Concentration:5 μM, 10 μM
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Incubation Time:24 h
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Result:Increased the apoptotic ratio from 4.1% (control) to 8.3% at 5 μM when used alone.
Increased the apoptotic ratio from 4.1% (control) to 22.2% at 10 μM when used alone.
Increased the apoptotic ratio from 13.5% (IR alone) to 19.4% at 5 μM when combined with 4 GY ionizing radiation (IR).
Increased the apoptotic ratio from 13.5% (IR alone) to 43.8% at 10 μM when combined with 4 GY IR.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c nude (male, 4-5 weeks old, 15-18 g, subcutaneous xenograft model)[1]
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Dosage:10 mg/kg
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Administration:i.p.; daily; 14 days
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Result:Slightly inhibited tumor growth alone.
Reduced tumor weight by 79% when combined with 1 GY IR.
Caused slight body weight loss relative to controls alone.
Showed no obvious body weight difference compared to IR alone group when combined with IR.
Exhibited protective effect on liver and spleen weight against IR-induced reduction.
Chemical Information
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CAS No. 3115524-78-9
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Molecular Weight 603.75
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Formula C34H45N5O5
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SMILES
CN(C)CCN1C(C2=CC(OC)=C(OCCCN3CCN(CCN(C)C)CC3)C=C2C4=C1C(C=C(OCO5)C5=C6)=C6C=C4)=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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