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TNG348
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Catalog No. T88075Cas No. 2839740-79-1
Alias TNG-348, TNG 348
TNG348 is an allosteric, selective, and reversible inhibitor of USP1, causing dose-dependent accumulation of ubiquitinated substrates in vitro and in vivo. CRISPR screens demonstrate that TNG348 disrupts DNA damage tolerance by interfering with the translesion synthesis pathway via RAD18-dependent ubiquitinated PCNA. Although both TNG348 and PARP inhibitors selectively kill homologous recombination-deficient tumors, they act through distinct mechanisms: PARP1 knockout confers resistance to PARP inhibitors but sensitizes cells to TNG348. Consistent with this mechanistic divergence, combining TNG348 with PARP inhibitors results in synergistic antitumor efficacy, including tumor growth inhibition and regression in multiple HRD mouse xenograft models.
TNG348
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Purity: 98.67%
Catalog No. T88075Alias TNG-348, TNG 348Cas No. 2839740-79-1
TNG348 is an allosteric, selective, and reversible inhibitor of USP1, causing dose-dependent accumulation of ubiquitinated substrates in vitro and in vivo. CRISPR screens demonstrate that TNG348 disrupts DNA damage tolerance by interfering with the translesion synthesis pathway via RAD18-dependent ubiquitinated PCNA. Although both TNG348 and PARP inhibitors selectively kill homologous recombination-deficient tumors, they act through distinct mechanisms: PARP1 knockout confers resistance to PARP inhibitors but sensitizes cells to TNG348. Consistent with this mechanistic divergence, combining TNG348 with PARP inhibitors results in synergistic antitumor efficacy, including tumor growth inhibition and regression in multiple HRD mouse xenograft models.
| Pack Size | Price | USA Warehouse | Global Warehouse | Quantity |
|---|---|---|---|---|
| 1 mg | $145 | - | In Stock | |
| 5 mg | $362 | - | In Stock | |
| 10 mg | $579 | - | In Stock | |
| 25 mg | $1,160 | - | In Stock | |
| 50 mg | $1,860 | - | In Stock | |
| 1 mL x 10 mM (in DMSO) | $479 | - | In Stock |
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In Stock Estimated shipping dateUSA Warehouse[1-2 days] Global Warehouse[5-7 days]
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Purity:98.67%
Appearance:Solid
Color:White
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Product Introduction
Bioactivity
Chemical Properties
Storage & Solubility Information
| Description | TNG348 is an allosteric, selective, and reversible inhibitor of USP1, causing dose-dependent accumulation of ubiquitinated substrates in vitro and in vivo. CRISPR screens demonstrate that TNG348 disrupts DNA damage tolerance by interfering with the translesion synthesis pathway via RAD18-dependent ubiquitinated PCNA. Although both TNG348 and PARP inhibitors selectively kill homologous recombination-deficient tumors, they act through distinct mechanisms: PARP1 knockout confers resistance to PARP inhibitors but sensitizes cells to TNG348. Consistent with this mechanistic divergence, combining TNG348 with PARP inhibitors results in synergistic antitumor efficacy, including tumor growth inhibition and regression in multiple HRD mouse xenograft models. |
| In vitro | TNG348 exhibits high selective inhibitory activity against USP1 in vitro, with an IC50 value of 98.5 nmol/L. Through cryo-electron microscopy structure determination of Broussonetia papyrifera, it was found that TNG348 binds to a cryptic allosteric pocket of USP1, non-competitively inhibiting its activity [1]. In MDA-MB-436 cells, TNG348 dose-dependently accumulates ubiquitinated PCNA and FANCD2, with an IC50 value of 98.6 nmol/L [1]. |
| In vivo | In the MDA-MB-436 tumor mouse model, TNG348 demonstrated favorable pharmacokinetic properties when administered orally at doses of 30 mg/kg once daily or 20 mg/kg twice daily, with plasma exposure levels exceeding the in vitro IC50 value for over 8 hours [1]. |
| Synonyms | TNG-348, TNG 348 |
| Molecular Weight | 603.52 |
| Formula | C27H23F6N9O |
| Cas No. | 2839740-79-1 |
| Smiles | FC(F)(F)C=1N=C(C=2C=CC(=CC2)CN3C4=NC(=NC=C4N(C3=N)CC(F)(F)F)C=5C(=NC=NC5C6CC6)OC)N(C1)C |
| Storage | store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. | |||||||||||||||||||||||||||||||||||
| Solubility Information | DMSO: 80 mg/mL (132.56 mM), Sonication is recommeded. | |||||||||||||||||||||||||||||||||||
Solution Preparation Table | ||||||||||||||||||||||||||||||||||||
DMSO
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Calculator
In Vivo Formulation Calculator (Clear solution)
Please enter your animal experiment information in the following box and click Calculate to obtain the stock solution preparation method and in vivo formula preparation method:
For example, if the intended dosage is 10 mg/kg for animals weighing 20 g , with a dosing volume of 100 μL per animal, and a total of 10 animals are to be administered, using a formulation of 
10% DMSO+ 40% PEG300+ 5% Tween 80+ 45% Saline/PBS/ddH2O , the resulting working solution concentration would be 2 mg/mL.Stock Solution Preparation:
Dissolve 2 mg of the compound in 100 μL DMSO to obtain a stock solution at a concentration of 20 mg/mL . If the required concentration exceeds the compound's known solubility, please contact us for technical support before proceeding.
Preparation of the In Vivo Formulation:
1) Add 100 μL of the DMSO stock solution to 400 μL PEG300 and mix thoroughly until the solution becomes clear.
2) Add 50 μL Tween 80 and mix well until fully clarified.
3) Add 450 μL Saline,PBS or ddH2O and mix thoroughly until a homogeneous solution is obtained.
This example is provided solely to demonstrate the use of the In Vivo Formulation Calculator and does not constitute a recommended formulation for any specific compound. Please select an appropriate dissolution and formulation strategy based on your experimental model and route of administration.
Dose Conversion
You can also refer to dose conversion for different animals. More Dose Conversion
Tech Support
Please see Inhibitor Handling Instructions for more frequently ask questions. Topics include: how to prepare stock solutions, how to store products, and cautions on cell-based assays & animal experiments, etc
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