I-138

SKU: orb1744068

Description

I-138 is a potent, cell-permeable inhibitor of the USP1-UAF1 deubiquitinase complex. It promotes the mono-ubiquitination of FANCD2 and PCNA, key DNA damage response proteins, and blocks USP1 auto-processing. This compound is a valuable tool for studying DNA repair pathways, replication stress, and the Fanconi anemia network in cellular models.

Research Area

Cell Biology, Molecular Biology, Protein Biochemistry

Key Properties

• CAS Number: 2098211-50-6
• MW: 492.5
• Purity: 99.41% (May vary between batches)
• Formula: C₂₆H₂₃F₃N₆O
• SMILES: C(N1C=2C(NC1=O)=CN=C(N2)C3=C(C(C)C)C=CC=C3)C4=CC=C(C=C4)C5=NC(C(F)(F)F)=CN5C
• Target: DUB
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:3.3 mg/mL (6.7 mM);DMSO:80 mg/mL (162.44 mM)

Bioactivity

• In Vivo:
  I-138 (50 mg/kg/day; oral administration; for 41 days) shows USP1 inhibition and moderate antitumor activity in mice with MDA-MB-436 tumors. However, combining I-138 with the PARP inhibitor Niraparib is more effective at inhibiting BRCA1/2 mutant tumors in vivo.
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• In Vitro:
  I-138 (0.5 μM; 4 hours) eliminates USP1 autodeubiquitination in HAP-1 USP1 WT and knockout cells, induces monoubiquitination of FANCD2 and PCNA in MDA-MB-436 cells, and dose-dependently (0.01-10 μM; 10 days) inhibits the viability of MDA-MB-436 cells without affecting HCC1954 cells.
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

USP1-UAF1

Compound Identifiers

PubChem CID

129139687