ArticleScience advances2022
Cryo-EM reveals a mechanism of USP1 inhibition through a cryptic binding site.
Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed.
- Discovery of a Potent Fluorescence Polarization Probe for Identifying USP1 Allosteric Inhibitors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Disrupting the USP1-UAF1 deubiquitinase complex: a master regulator of replication stress and frontier target in cancer therapy.Medical oncology (Northwood, London, England) · 2026Review
- Serum USP1 and PD-L1 levels independently predict treatment response and prognosis in cervical cancer: a retrospective cohort study.American journal of cancer research · 2026Article
- Cell type-specific functions of the PBAF chromatin-remodeling complex in neuronal diversification.Nature communications · 2025Article
- Chimeric deubiquitinase engineering reveals structural basis for specific inhibition of the mitophagy regulator USP30.Nature structural & molecular biology · 2025Article
- Molecular glues that inhibit deubiquitylase activity and inflammatory signaling.Nature structural & molecular biology · 2025Article
- USP1 inhibition: A journey from target discovery to clinical translation.Pharmacology & therapeutics · 2025Review
- A large-scale curated and filterable dataset for cryo-EM foundation model pre-training.Scientific data · 2025Article
- Characterization of TNG348: A Selective, Allosteric USP1 Inhibitor That Synergizes with PARP Inhibitors in Tumors with Homologous Recombination Deficiency.Molecular cancer therapeutics · 2025Article
- Harnessing the Deubiquitinase USP1 for Targeted Protein Stabilization.Journal of the American Chemical Society · 2025Article
- Targeting USP1 Potentiates Radiation-Induced Type I IFN-Dependent Antitumor Immunity by Enhancing Oligo-Ubiquitinated SAR1A-Mediated STING Trafficking and Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Emerging frontiers in protein structure prediction following the AlphaFold revolution.Journal of the Royal Society, Interface · 2025Review
- A structure-based framework for selective inhibitor design and optimization.Communications biology · 2025Article
- Ubiquitin-Specific Protease Inhibitors for Cancer Therapy: Recent Advances and Future Prospects.Biomolecules · 2025Review
- USP1 deubiquitinates PARP1 to regulate its trapping and PARylation activity.Science advances · 2024Article
- Molecular glues that inhibit deubiquitylase activity and inflammatory signalling.bioRxiv : the preprint server for biology · 2024Article
- Structural and Biochemical Insights into the Mechanism of Action of the Clinical USP1 Inhibitor, KSQ-4279.Journal of medicinal chemistry · 2024Article
- New Horizons of Synthetic Lethality in Cancer: Current Development and Future Perspectives.Journal of medicinal chemistry · 2024Review
- DoUBLing up: ubiquitin and ubiquitin-like proteases in genome stability.The Biochemical journal · 2024Review
- Variety in the USP deubiquitinase catalytic mechanism.Life science alliance · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
Abstract
Repair of DNA damage is critical to genomic integrity and frequently disrupted in cancers. Ubiquitin-specific protease 1 (USP1), a nucleus-localized deubiquitinase, lies at the interface of multiple DNA repair pathways and is a promising drug target for certain cancers. Although multiple inhibitors of this enzyme, including one in phase 1 clinical trials, have been established, their binding mode is unknown. Here, we use cryo-electron microscopy to study an assembled enzyme-substrate-inhibitor complex of USP1 and the well-established inhibitor, ML323. Achieving 2.5-Å resolution, with and without ML323, we find an unusual binding mode in which the inhibitor disrupts part of the hydrophobic core of USP1. The consequent conformational changes in the secondary structure lead to subtle rearrangements in the active site that underlie the mechanism of inhibition. These structures provide a platform for structure-based drug design targeting USP1.
Identifiers
What OpenQuestion holds
Registered trials
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.