TDG-IN-1
TDG-IN-1 is an orally active, selective small-molecule inhibitor of thymine DNA glycosylase (TDG) with a Ka of 1.46 nM. TDG-IN-1 impairs the DNA-binding ability of TDG, induces downregulated expression of DHX9, accumulation of double-stranded RNA, and activation of the RIG-I/MDA5-MAVS pathway, while acting as a tumor suppressor, innate immune activator and immunostimulant. TDG-IN-1 inhibits the growth of p53-deficient tumor cells and xenograft tumors, and exerts a synthetic lethal effect with p53. TDG-IN-1 is applicable to the research of p53-deficient cancers.
For research use only. We do not sell to patients.
- CAS No.: 3092641-80-7
- Formula: C13H14O4
- Molecular Weight:234.25
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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
- Purity & Documentation
- References
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Help & FAQs
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Biological Activity
TDG-IN-1 (Compound C-271) (0.16-0.25 μM; 1 h at 30 °C) potently inhibits the glycosylase activity of purified human TDG across multiple dsDNA substrates, with IC50 values ranging from 0.16 to 0.25 μM[1].
TDG-IN-1 (0.11-0.19 μM; overnight at 4 °C) blocks TDG's ability to bind dsDNA across multiple substrate types, with IC50 values ranging from 0.11 to 0.19 μM[1].
TDG-IN-1 (1.25 μM; 4 days) suppresses the viability of p53-deficient KP lung adenocarcinoma cells in a TDG-dependent manner[1].
TDG-IN-1 (0.04-30 μM; 144 h) selectively inhibits the viability of p53-deficient human solid cancer cell lines, with IC50 values below 5 μM for 16 tested p53-deficient lines[1].
TDG-IN-1 (1.25 μM; 4 days) treatment of p53-deficient KP lung adenocarcinoma cells leads to accumulation of cytoplasmic dsRNA[1].
TDG-IN-1 (0.625-2.5 μM; 4 days) downregulates DHX9 protein expression in p53-deficient KP lung adenocarcinoma cells in vitro in a dose-dependent manner[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Mouse KP (Kras^{LSL-G12D/+}; Trp53^{flox/flox}) lung adenocarcinoma cells
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Concentration:1.25 μM (follow-up experiments); IC50 range tested
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Incubation Time:4 days (follow-up experiments)
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Result:Selectively inhibited the viability of wild-type KP cells, with this effect attenuated in TDG-KO and TDG^{C287S} (mouse ortholog of human C276S) mutant KP cells.
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Cell Line:Mouse KP lung adenocarcinoma cells
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Concentration:1.25 μM
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Incubation Time:4 days
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Result:Induced a significant increase in cytoplasmic dsRNA accumulation in KP cells; this signal was abolished by RNase III treatment.
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Cell Line:Mouse KP lung adenocarcinoma cells
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Concentration:0.625, 1.25, 2.5 μM
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Incubation Time:4 days
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Result:Dose-dependently reduced DHX9 protein levels in KP cells.
TDG-IN-1 (5 mg/kg; i.g.; once daily for 30-50 days) synergizes with anti-CTLA4 antibody to enhance the inhibitory effect on tumor growth and prolong the survival of mice bearing p53-deficient KP allograft tumor models[1].
TDG-IN-1 (5 mg/kg; i.g.; once daily for 25-50 days) acts synergistically with anti-CTLA4 antibody to enhance the inhibitory effect on tumor growth and prolong survival in p53-deficient 4T1 breast cancer xenograft models[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Nude mice (female, 6-8 weeks old)[1]
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Dosage:50 mg/kg
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Administration:i.g.; once daily for 14-25 days
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Result:Suppressed p53-deficient tumors growth and induced
cytoplasmic dsRNA accumulation.
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Animal Model:C57BL/6 mice (female, 6-8 weeks old)[1]
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Dosage:5 mg/kg
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Administration:i.g.; once daily for 30-50 days
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Result:Produced enhanced tumor growth inhibition compared to either agent alone when combined with anti-CTLA4 antibody.
Prolonged mouse survival.
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Animal Model:BALB/c mice (female, 6-8 weeks old)[1]
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Dosage:5 mg/kg
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Administration:i.g.; once daily for 25-50 days
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Result:Produced enhanced tumor growth inhibition compared to either agent alone when combined with anti-CTLA4 antibody.
Prolonged mouse survival.
Chemical Information
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CAS No. 3092641-80-7
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Molecular Weight 234.25
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Formula C13H14O4
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SMILES
O=C1C2CC2C(C3=CC(C)=C(O)C=C3OC)O1
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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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