ArticleScientific reports2020
Selective USP7 inhibition elicits cancer cell killing through a p53-dependent mechanism.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 115 citations in OpenAlex.
- Balancing Ubiquitination and Deubiquitination in Apoptotic Protein Stability and Cancer Cell Survival.International journal of molecular sciences · 2026Review
- FLT3-ITD signals for CEBPA and p53 proteolysis by the ubiquitin-proteosome pathway.Research square · 2026Article
- FLT3-ITD signals for CEBPA and p53 proteolysis by the ubiquitin-proteosome pathway.bioRxiv : the preprint server for biology · 2026Article
- Inhibition of USP7 Destabilizes the Noncanonical PRC1.1 Complex and Induces Neuroblastoma Differentiation.Molecular cancer research : MCR · 2026Article
- Proteome-wide Ubiquitinome Profiling Reveals Substrate-specific Dynamics Within the USP7 Network.Molecular & cellular proteomics : MCP · 2026Article
- USP7 inhibition perturbs proteostasis and tumorigenesis in triple-negative breast cancer.NPJ breast cancer · 2026Article
- Targeted degradation of USP7 in solid cancer cells reveals distinct effects of deubiquitinase degraders and inhibitors.Nature communications · 2026Article
- Assessing the suitability of deubiquitylases as substrates for targeted protein degradation.Cell chemical biology · 2026Article
- Targeting DESI2 as a Novel Therapeutic Strategy for JAK2-Mutant Leukemias.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The role of USP19 in human diseases: from molecular function to clinical relevance.Frontiers in immunology · 2026Review
- Review
- Small-molecule allosteric activator of ubiquitin-specific protease 7 (USP7).Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- USP7 at the Crossroads of Ubiquitin Signaling, Cell Cycle, and Tumorigenesis.Molecules (Basel, Switzerland) · 2025Review
- Proteostasis of immune checkpoint receptors.The Biochemical journal · 2025Review
- Pharmacologic interrogation of USP28 cellular function in p53 signaling.Cell chemical biology · 2025Article
- Design, Synthesis, and Molecular Evaluation of SArchiv der Pharmazie · 2025Article
- Chromatin Perturbation Promotes Susceptibility to Hypomethylating Agents.bioRxiv : the preprint server for biology · 2025Article
- AKT and DUBs: a bidirectional relationship.Cellular & molecular biology letters · 2025Review
- Targeted protein degradation for cancer therapy.Nature reviews. Cancer · 2025Review
- Targeting MYC: Multidimensional regulation and therapeutic strategies in oncology.Genes & diseases · 2025Review
12 more citing papers are in PubMed but not listed here.
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Authors and funding
27 authors at 7 institutions in 2 countries.
Funding
Abstract
Ubiquitin specific peptidase 7 (USP7) is a deubiquitinating enzyme (DUB) that removes ubiquitin tags from specific protein substrates in order to alter their degradation rate and sub-cellular localization. USP7 has been proposed as a therapeutic target in several cancers because it has many reported substrates with a role in cancer progression, including FOXO4, MDM2, N-Myc, and PTEN. The multi-substrate nature of USP7, combined with the modest potency and selectivity of early generation USP7 inhibitors, has presented a challenge in defining predictors of response to USP7 and potential patient populations that would benefit most from USP7-targeted drugs. Here, we describe the structure-guided development of XL177A, which 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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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.