TDG-IN-1 

TDG-IN-1 is an orally active, selective small-molecule inhibitor of thymine DNA glycosylase (TDG) with a K_a 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^[1].

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.

TDG-IN-1 (Compound C-271) (50 mg/kg; i.g.; once daily for 14-20 days) induces a 79% tumor growth inhibition rate in p53-null NCI-H1299 xenograft models, extends the survival time of mice, and causes no obvious toxicity^[1].
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.

234.25

C₁₃H₁₄O₄

3092641-80-7

O=C1C2CC2C(C3=CC(C)=C(O)C=C3OC)O1

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Zhou JX, et al. Targeting thymine DNA glycosylase induces synthetic lethality in p53-deficient cancers. Nat Chem Biol. Published online January 22, 2026.  [Content Brief]