ArticleMolecular cancer therapeutics2013
Small-molecule inhibitors of USP1 target ID1 degradation in leukemic cells.
Article in Molecular cancer therapeutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers, 1 of them a synthesis that pooled it.
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Who cites it
111 citing papers in PubMed, 1 synthesis or guideline pooled it, 170 citations in OpenAlex.
- Pooled it
- 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
- The Potential Role of Deubiquitinating Enzymes (DUBs) in Male Fertility.Biomolecules · 2026Review
- CHK1 inhibition rescues abnormal glycogen buildup in a Caenorhabditis elegans model for glycogen storage disease III.Communications biology · 2026Article
- ID1 in hematopoiesis and hematologic disorders: novel potentials of a classic differentiation regulator.Cellular & molecular biology letters · 2025Review
- UCHL3: a crucial deubiquitinase in DNA damage repair and tumor progression.Cancer cell international · 2025Review
- Key roles of ubiquitination in regulating critical regulators of cancer stem cell functionality.Genes & diseases · 2025Review
- Harnessing the Deubiquitinase USP1 for Targeted Protein Stabilization.Journal of the American Chemical Society · 2025Article
- Ubiquitin-Specific Protease Inhibitors for Cancer Therapy: Recent Advances and Future Prospects.Biomolecules · 2025Review
- The other side of the coin: protein deubiquitination by Ubiquitin-Specific Protease 1 in cancer progression and therapy.Future medicinal chemistry · 2025Review
- Recurrent Missense Driver STAT5BAnti-cancer agents in medicinal chemistry · 2025Article
- The antipsychotic drug pimozide promotes apoptosis through the RAF/ERK pathway and enhances autophagy in breast cancer cells.Cancer biology & therapy · 2024Article
- The USP1 Inhibitor KSQ-4279 Overcomes PARP Inhibitor Resistance in Homologous Recombination-Deficient Tumors.Cancer research · 2024Article
- The role of ubiquitination in health and disease.MedComm · 2024Review
- Structural and Biochemical Insights into the Mechanism of Action of the Clinical USP1 Inhibitor, KSQ-4279.Journal of medicinal chemistry · 2024Article
- Drug resistance mechanisms and treatment strategies mediated by Ubiquitin-Specific Proteases (USPs) in cancers: new directions and therapeutic options.Molecular cancer · 2024Review
- Interfering with the AKT/mTOR/STAT3/ID1 signaling axis with usenamine A restrains the proliferative and invasive potential of human hepatocellular carcinoma cells.Chinese medicine · 2024Article
- Role of Ubiquitin-specific Proteases in Hepatocellular Carcinoma Pathogenesis.Current topics in medicinal chemistry · 2024Review
- Deubiquitylating Enzymes in Cancer and Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
51 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Inhibitor of DNA binding 1 (ID1) transcription factor is essential for the proliferation and progression of many cancer types, including leukemia. However, the ID1 protein has not yet been therapeutically targeted in leukemia. ID1 is normally polyubiquitinated and degraded by the proteasome. Recently, it has been shown that USP1, a ubiquitin-specific protease, deubiquitinates ID1 and rescues it from proteasome degradation. Inhibition of USP1 therefore offers a new avenue to target ID1 in cancer. Here, using a ubiquitin-rhodamine-based high-throughput screening, we identified small-molecule inhibitors of USP1 and investigated their therapeutic potential for leukemia. These inhibitors blocked the deubiquitinating enzyme activity of USP1 in vitro in a dose-dependent manner with an IC50 in the high nanomolar range. USP1 inhibitors promoted the degradation of ID1 and, concurrently, inhibited the growth of leukemic cell lines in a dose-dependent manner. A known USP1 inhibitor, pimozide, also promoted ID1 degradation and inhibited growth of leukemic cells. In addition, the growth of primary acute myelogenous leukemia (AML) patient-derived leukemic cells was inhibited by a USP1 inhibitor. Collectively, these results indicate that the novel small-molecule inhibitors of USP1 promote ID1 degradation and are cytotoxic to leukemic cells. The identification of USP1 inhibitors therefore opens up a new approach for leukemia therapy.
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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.