XL177A

SKU: orb1298350

Description

XL177A is a potent and selective irreversible inhibitor of USP7 with an IC50 of 0.34 nM. Its anti-cancer activity is mediated through p53-dependent apoptosis, making it a valuable chemical probe for studying ubiquitination pathways in oncology research, both in vitro and in vivo.

Research Area

Cell Biology, Molecular Biology, Protein Biochemistry

Key Properties

• CAS Number: 2417089-74-6
• MW: 861.47
• Purity: 98.75% (May vary between batches)
• Formula: C₄₈H₅₇ClN₈O₅
• SMILES: CN1CCN(CCC(=O)Nc2ccc3c(c2)ncn(CC2(O)CCN(CC2)C(=O)[C@@H](CCCNC(=O)c2ccc4c(Cl)c5CCCCc5nc4c2)Cc2ccccc2)c3=O)CC1
• Target: DUB
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (2.32 mM);DMSO:55 mg/mL (63.84 mM)

Bioactivity

• Target IC50:
  USP7:0.34 nM
• In Vitro:
  XL177A irreversibly inhibits USP7 with sub-nM potency and selectivity across the human proteome. Evaluation of the cellular effects of XL177A reveals that selective USP7 inhibition suppresses cancer cell growth predominantly through a p53-dependent mechanism: XL177A specifically upregulates p53 transcriptional targets transcriptome-wide, hotspot mutations in TP53 but not any other genes predict response to XL177A across a panel of ~500 cancer cell lines, and TP53 knockout rescues XL177A-mediated growth suppression of TP53 wild-type (WT) cells. Together, these findings suggest TP53 mutational status as a biomarker for response to USP7 inhibition. We find that Ewing sarcoma and malignant rhabdoid tumor (MRT), two pediatric cancers that are sensitive to other p53-dependent cytotoxic drugs, also display increased sensitivity to XL177A.
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Storage & Handling

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

Alternative Names

DUBs, Deubiquitinase, cancer, inhibit, p53, Inhibitor, MCF7, XL177A, XL-177A, USP7

Compound Identifiers

PubChem CID

153002269