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TNG348

CAT: 0931-T88075-01Size: 1 mgDry Ice: NoHazardous: No
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CAT#:0931-T88075-01Size:1 mg
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24/48H Stock Items & 2 to 6 Weeks non Stock Items.
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CAS Number
2839740-79-1
Target
DUB
Related Pathways
Cell Cycle/Checkpoint, Ubiquitination, DNA Damage/DNA Repair
Purity
0.9867
Bioactivity
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.
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
Molecular Formula
C27H23F6N9O
Molecular Weight
603.52
Shipping Conditions
Ice Packs
Storage Temperature
-20°C

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