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.
All DNA/RNA Synthesis Isoforms
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Biological Activity
Description
In Vitro
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. Further protocols information, click here.
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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.
In Vivo
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.
Protocols
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RNA extraction experimental
By lysing cells, releasing RNA, and removing impurities such as proteins and DNA, high-purity RNA products are finally obtained. The commonly used traditional method is the guanidine isothiocyanate/phenol/chloroform method (Trizol), which is suitable for a variety of animal materials including animal tissues, microorganisms, cultured cells, etc., and most plant materials.
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Patient-Derived Xenograft (PDX)
Patient-derived xenograft (PDX) models are generated by engrafting primary human tumor tissue directly into immunodeficient mice, allowing in vivo propagation of patient tumor biology without initial in vitro adaptation. These models are used to preserve key histopathological and molecular characteristics of the original tumor and enable assessment of tumor growth dynamics and therapeutic response in a living organism. The biological readout is tumor engraftment and subsequent growth in the murine host, which reflects the ability of human tumor cells to survive, vascularize, and expand in an immunocompromised microenvironment.
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Splenic/Portal-Vein Liver Metastasis Xenograft
Splenic and portal-vein liver metastasis xenograft models deliver tumor cells into the portal circulation so that cells reach the liver first and form hepatic metastatic lesions; splenic injection uses the spleen as an access route to the portal system, while direct portal-vein injection introduces cells into the portal vein without requiring splenectomy. The assay detects liver colonization, intrahepatic tumor growth, tumor distribution, treatment response, survival, and liver-metastasis microenvironment changes; readouts include bioluminescence or fluorescence imaging, gross liver nodule counts, liver weight or tumor burden, histology, and survival.
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Subcutaneous Cell-Line-Derived Xenograft
Subcutaneous cell-line-derived xenograft (CDX) models are established by implanting cultured human cancer cell lines into immunodeficient mice, where the injected cells form localized tumors that can be monitored in vivo as a measure of tumorigenic potential, growth kinetics, and treatment response. These models are widely used in oncology research because they allow reproducible tumor formation and enable comparative assessment of tumor growth between different cell lines or genetic manipulations in a controlled in vivo microenvironment. Subcutaneous implantation of cancer cells in immunodeficient mice is a standard approach for evaluating tumor growth behavior and therapeutic response across multiple cancer types, including prostate, esophageal, pancreatic, and colon cancer models.
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Orthotopic Cell-Line Xenograft
Orthotopic cell-line xenograft models involve implantation of human cancer cell lines into the anatomically corresponding organ of immunodeficient mice to reproduce tumor growth within a native microenvironment, enabling more clinically relevant tumor behavior compared with subcutaneous models. These models are widely used because orthotopic placement better recapitulates tumor progression, including invasion and metastatic spread, which are often underrepresented in heterotopic implantation systems. Compared with conventional xenografts, orthotopic implantation is described as more technically complex but provides improved simulation of tumor-microenvironment interactions and metastatic behavior, making it particularly valuable for translational oncology research. Surgical orthotopic implantation approaches have been emphasized as enabling faithful reproduction of clinical cancer features, including metastasis and disease progression patterns that align with the tumor’s organ of origi
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Intraperitoneal/Peritoneal Dissemination Xenograft
Intraperitoneal (IP) or peritoneal dissemination xenograft models are based on the introduction of human cancer cells into the peritoneal cavity of immunodeficient mice, where they attach to peritoneal surfaces, form multicellular aggregates or spheroids, and progressively generate disseminated tumor nodules that mimic advanced peritoneal metastatic disease. These models are widely used to study ovarian cancer progression, tumor-microenvironment interactions, and intraperitoneal therapeutic responses, often incorporating bioluminescence or fluorescence imaging to longitudinally monitor tumor burden in vivo. The biological principle relies on the capacity of tumor cells such as SKOV3 or related ovarian carcinoma lines to survive in suspension, aggregate within ascites-like fluid, adhere to mesothelial surfaces, and invade peritoneal organs, thereby recapitulating human peritoneal carcinomatosis patterns observed in advanced disease.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)