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TNG348

SKU: orb2564618

Description

TNG348 is a selective, reversible USP1 inhibitor that disrupts RAD18-dependent translesion synthesis, leading to ubiquitinated substrate accumulation. It exhibits synergistic antitumor activity with PARP inhibitors in HR-deficient models, offering a distinct mechanism for targeting DNA damage repair pathways in cancer research.

Research Area

Cell Biology, Molecular Biology, Protein Biochemistry

Images & Validation

Key Properties

CAS Number2839740-79-1
MW603.52
Purity98.67%
FormulaC27H23F6N9O
SMILESFC(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
TargetDUB
SolubilityDMSO:80 mg/mL (132.56 mM)

Bioactivity

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 .
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 . In MDA-MB-436 cells, TNG348 dose-dependently accumulates ubiquitinated PCNA and FANCD2, with an IC50 value of 98.6 nmol/L .

Storage & Handling

Storagestore at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice.
Expiration Date12 months from date of receipt.
DisclaimerFor research use only

Alternative Names

TNG 348, TNG-348
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Quality Guarantee

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Key Properties

No computed properties available.

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Protocol Information

TNG348 (orb2564618)

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Available Sizes

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1 mg
$ 190.00
5 mg
$ 410.00
1 ml x 10 mM (in DMSO)
$ 520.00
10 mg
$ 620.00
25 mg
$ 1,200.00
50 mg
$ 1,900.00
DispatchUsually dispatched within 5-10 working days
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