ArticleProceedings of the National Academy of Sciences of the United States of America2022
Mechanism-based heparanase inhibitors reduce cancer metastasis in vivo.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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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.
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Who cites it
23 citing papers in PubMed, 46 citations in OpenAlex.
- Brain targeting and trafficking of extracellular vesicles in central nervous system diseases: a therapeutic roadmap.Nanomedicine (London, England) · 2026Review
- Identification of targets of clinical FOXA1 mutants involved in EMT and immune suppression in prostate cancer.Communications biology · 2026Article
- An integral membrane constitutively active heparanase enhances the tumor infiltration capability of NK cells.Oncoimmunology · 2025Article
- From Native Glycosaminoglycans to Mimetics: Design, Mechanisms, and Biomedical Applications.Biomolecules · 2025Review
- Heparanase 2 Modulates Vascular Permeability via Heparan Sulfate-Dependent Growth Factor Signaling.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Unlocking longevity through the comparative biology of aging.Nature aging · 2025Review
- The First Simplified Heparan Sulphate-Alginate Hybrid Trisaccharides: Synthesis and Biological Effects on Human Dermal Fibroblasts.International journal of molecular sciences · 2025Article
- Activity-based probes for dynamic characterisation of polysaccharide-degrading enzymes.The Biochemical journal · 2025Review
- Design of Paromomycin and Neomycin as Sulfated and Hydrophobic Glycans to Target Heparanase-Driven Tumor Progression and Metastasis.Journal of medicinal chemistry · 2025Article
- Structural glycobiology - from enzymes to organelles.Biochemical Society transactions · 2025Review
- Activity-Based Profiling of Retaining Glycosidases in Disease Diagnosis and Their Application in Drug Discovery.Handbook of experimental pharmacology · 2025Review
- From Mechanism-Based Retaining Glycosidase Inhibitors to Activity-Based Glycosidase Profiling.Journal of the American Chemical Society · 2024Review
- Splice Variant ofGenes · 2024Article
- Design Principle of Heparanase Inhibitors: A Combined In Vitro and In Silico Study.ACS medicinal chemistry letters · 2024Article
- A New Synthesized Dicarboxylated Oxy-Heparin Efficiently Attenuates Tumor Growth and Metastasis.Cells · 2024Article
- Molecular Basis for Inhibition of Heparanases and β-Glucuronidases by Siastatin B.Journal of the American Chemical Society · 2024Article
- Synthetic Heparanase Inhibitors Can Prevent Herpes Simplex Viral Spread.Angewandte Chemie (International ed. in English) · 2023Article
- A New Paradigm in the Relationship between Gut Microbiota and Breast Cancer: β-glucuronidase Enzyme Identified as Potential Therapeutic Target.Pathogens (Basel, Switzerland) · 2023Review
- Heparanase-A single protein with multiple enzymatic and nonenzymatic functions.Proteoglycan research · 2023Review
- 4-O-Substituted Glucuronic Cyclophellitols are Selective Mechanism-Based Heparanase Inhibitors.ChemMedChem · 2023Article
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 4 countries.
Funding
Abstract
Heparan sulfate proteoglycans (HSPGs) mediate essential interactions throughout the extracellular matrix (ECM), providing signals that regulate cellular growth and development. Altered HSPG composition during tumorigenesis strongly aids cancer progression. Heparanase (HPSE) is the principal enzyme responsible for extracellular heparan sulfate catabolism and is markedly up-regulated in aggressive cancers. HPSE overactivity degrades HSPGs within the ECM, facilitating metastatic dissemination and releasing mitogens that drive cellular proliferation. Reducing extracellular HPSE activity reduces cancer growth, but few effective inhibitors are known, and none are clinically approved. Inspired by the natural glycosidase inhibitor cyclophellitol, we developed nanomolar mechanism-based, irreversible HPSE inhibitors that are effective within physiological environments. Application of cyclophellitol-derived HPSE inhibitors reduces cancer aggression in cellulo and significantly ameliorates murine metastasis. Mechanism-based irreversible HPSE inhibition is an unexplored anticancer strategy. We demonstrate the feasibility of such compounds to control pathological HPSE-driven malignancies.
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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.