ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014
Small-molecule RA-9 inhibits proteasome-associated DUBs and ovarian cancer in vitro and in vivo via exacerbating unfolded protein responses.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.Pharmacology & therapeutics · 2020Pooled it
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- Deubiquitinating enzymes in parkinson's disease: molecular mechanisms and therapeutic potential.Molecular medicine (Cambridge, Mass.) · 2025Review
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- NSC632839 suppresses esophageal squamous cell carcinoma cell proliferation in vitro by triggering spindle assembly checkpoint-mediated mitotic arrest and CREB-Noxa-dependent apoptosis.Cancer cell international · 2025Article
- Ubiquitin-Specific Protease Inhibitors for Cancer Therapy: Recent Advances and Future Prospects.Biomolecules · 2025Review
- DUBs in Alzheimer's disease: mechanisms and therapeutic implications.Cell death discovery · 2024Review
- Exploring the Role of Ubiquitin-Proteasome System in the Pathogenesis of Parkinson's Disease.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Deubiquitinases in Ovarian Cancer: Role in Drug Resistance and Tumor Aggressiveness.International journal of biological sciences · 2024Review
- Inhibition of USP1 activates ER stress through Ubi-protein aggregation to induce autophagy and apoptosis in HCC.Cell death & disease · 2022Article
- Proteotoxic stress-induced apoptosis in cancer cells: understanding the susceptibility and enhancing the potency.Cell death discovery · 2022Article
- Two novel piperidones induce apoptosis and antiproliferative effects on human prostate and lymphoma cancer cell lines.Investigational new drugs · 2022Article
- Ubiquitin specific peptidase 11 as a novel therapeutic target for cancer management.Cell death discovery · 2022Review
- Comprehensive Target Screening and Cellular Profiling of the Cancer-Active Compound b-AP15 Indicate Abrogation of Protein Homeostasis and Organelle Dysfunction as the Primary Mechanism of Action.Frontiers in oncology · 2022Article
- Pharmacological Modulation of Ubiquitin-Proteasome Pathways in Oncogenic Signaling.International journal of molecular sciences · 2021Review
- Deubiquitinases in hematological malignancies.Biomarker research · 2021Review
- Ubiquitin-Specific Proteases: Players in Cancer Cellular Processes.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Targeting the Ubiquitin-Proteasome System for Cancer Therapeutics by Small-Molecule Inhibitors.Cancers · 2021Review
- Repurposing old drugs as new inhibitors of the ubiquitin-proteasome pathway for cancer treatment.Seminars in cancer biology · 2021Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
purposeOvarian cancer is the deadliest of the gynecologic malignancies. Carcinogenic progression is accompanied by upregulation of ubiquitin-dependent protein degradation machinery as a mechanism to compensate with elevated endogenous proteotoxic stress. Recent studies support the notion that deubiquitinating enzymes (DUB) are essential factors in proteolytic degradation and that their aberrant activity is linked to cancer progression and chemoresistance. Thus, DUBs are an attractive therapeutic target for ovarian cancer. EXPERIMENTAL
designThe potency and selectivity of RA-9 inhibitor for proteasome-associated DUBs was determined in ovarian cancer cell lines and primary cells. The anticancer activity of RA-9 and its mechanism of action were evaluated in multiple cancer cell lines in vitro and in vivo in immunodeficient mice bearing an intraperitoneal ES-2 xenograft model of human ovarian cancer.
resultsHere, we report the characterization of RA-9 as a small-molecule inhibitor of proteasome-associated DUBs. Treatment with RA-9 selectively induces onset of apoptosis in ovarian cancer cell lines and primary cultures derived from donors. Loss of cell viability following RA-9 exposure is associated with an unfolded protein response as mechanism to compensate for unsustainable levels of proteotoxic stress. In vivo treatment with RA-9 retards tumor growth, increases overall survival, and was well tolerated by the host.
conclusionsOur preclinical studies support further evaluation of RA-9 as an ovarian cancer therapeutic.
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