ArticleAngewandte Chemie (International ed. in English)2018
Leveraging γ-Glutamyl Transferase To Direct Cytotoxicity of Copper Dithiocarbamates against Prostate Cancer Cells.
Article in Angewandte Chemie (International ed. in English), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 71 citations in OpenAlex.
- Bidentate Metal-Binding Motifs in US FDA Approved Small Molecule Drugs.Journal of medicinal chemistry · 2026Review
- Cuproptosis in prostate cancer: Molecular mechanisms, prognostic biomarkers and therapeutic frontiers of cuproptosis‑related genes (Review).International journal of oncology · 2025Review
- Cuproplasia and cuproptosis in hepatocellular carcinoma: mechanisms, relationship and potential role in tumor microenvironment and treatment.Cancer cell international · 2025Review
- Programmable "triple attack" cancer therapy throughChemical science · 2024Article
- Nanomedicine-based disulfiram and metal ion co-delivery strategies for cancer treatment.International journal of pharmaceutics: X · 2024Review
- A novel bioresponsive self-immolative spacer based on aza-quinone methide reactivity for the controlled release of thiols, phenols, amines, sulfonamides or amides.Chemical science · 2024Article
- Tumor microenvironment-activated theranostic nanoreactor for NIR-II Photoacoustic imaging-guided tumor-specific photothermal therapy.Fundamental research · 2024Article
- Design of Tetrazolium Cations for the Release of Antiproliferative Formazan Chelators in Mammalian Cells.Journal of the American Chemical Society · 2023Article
- Comparison of Serum Gamma Glutamyl Transferase Levels between Prostate Cancer Patients and Their Healthy Peers.Iranian journal of public health · 2023Article
- The immunomodulatory function and antitumor effect of disulfiram: paving the way for novel cancer therapeutics.Discover oncology · 2023Review
- Advancing Cancer Therapy with Copper/Disulfiram Nanomedicines and Drug Delivery Systems.Pharmaceutics · 2023Review
- New anti-cancer explorations based on metal ions.Journal of nanobiotechnology · 2022Review
- Selective Targeting of Cancer Cells by Copper Ionophores: An Overview.Frontiers in molecular biosciences · 2022Review
- N-Acetyl-l-cysteine restores reproductive defects caused by Ggt1 deletion in mice.Clinical and translational medicine · 2021Article
- Transcriptional Induction of Cystathionine γ-Lyase, a Reactive Sulfur-Producing Enzyme, by Copper Diethyldithiocarbamate in Cultured Vascular Endothelial Cells.International journal of molecular sciences · 2020Article
- Dithiocarbamate prodrugs activated by prostate specific antigen to target prostate cancer.Bioorganic & medicinal chemistry letters · 2020Article
- Self-triggered click reaction in an Alzheimer's disease model:Chemical science · 2019Article
- Emerging Opportunities To Manipulate Metal Trafficking for Therapeutic Benefit.Inorganic chemistry · 2019Review
- Introduction of the α-ketoamide structure: en route to develop hydrogen peroxide responsive prodrugs.Chemical science · 2019Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
A prodrug approach is presented to direct copper-dependent cytotoxicity to prostate cancer cells. The prochelator GGTDTC requires activation by γ-glutamyl transferase (GGT) to release the metal chelator diethyldithiocarbamate from a linker that masks its thiol reactivity and metal binding properties. In vitro studies demonstrated successful masking of copper binding as well as clean liberation of the chelator by GGT. GGTDTC was stable to non-specific degradation when incubated with a series of prostate cancer and normal cell lines, with selective release of diethyldithiocarbamate only occurring in cells with measurable GGT activity. The antiproliferative efficacy of the prochelator correlated with cellular GGT activity, with 24 h inhibitory concentrations ranging from 800 nm in prostate cancer lines 22Rv1 and LNCaP to over 15 μm in normal prostate PWR-1E cells. These findings underscore a new strategy to leverage the amplified copper metabolism of prostate cancer by conditional activation of a metal-binding pharmacophore.
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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.