ArticleBiochemical pharmacology2016
Platinum-containing compound platinum pyrithione is stronger and safer than cisplatin in cancer therapy.
Article in Biochemical pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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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
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Who cites it
20 citing papers in PubMed, 37 citations in OpenAlex.
- Ubiquitin-specific proteases in ovarian cancer: molecular mechanisms and therapeutic implications.Journal of ovarian research · 2026Review
- Ubiquitin-Specific Protease Inhibitors for Cancer Therapy: Recent Advances and Future Prospects.Biomolecules · 2025Review
- USP3 promotes osteosarcoma progression via deubiquitinating EPHA2 and activating the PI3K/AKT signaling pathway.Cell death & disease · 2024Article
- Investigating the anticancer properties of the two new platinum complexes with iso- and tert-pentylglycine by the DFT, molecular docking, and ADMET assessment and experimental confirmations.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2021Article
- Advances in the Development Ubiquitin-Specific Peptidase (USP) Inhibitors.International journal of molecular sciences · 2021Review
- Repurposing old drugs as new inhibitors of the ubiquitin-proteasome pathway for cancer treatment.Seminars in cancer biology · 2021Review
- Spectral, Molecular Modeling, and Biological Activity Studies on New Schiff's Base of Acenaphthaquinone Transition Metal Complexes.Bioinorganic chemistry and applications · 2021Article
- Targeting Ubiquitin-Proteasome System With Copper Complexes for Cancer Therapy.Frontiers in molecular biosciences · 2021Review
- USP14: Structure, Function, and Target Inhibition.Frontiers in pharmacology · 2021Review
- Replica exchange molecular dynamics simulation of the coordination of Pt(ii)-Phenanthroline to amyloid-β.RSC advances · 2019Article
- Crinamine Induces Apoptosis and Inhibits Proliferation, Migration, and Angiogenesis in Cervical Cancer SiHa Cells.Biomolecules · 2019Article
- Diplatin, a Novel and Low-Toxicity Anti-Lung Cancer Platinum Complex, Activation of Cell Death in TumorsFrontiers in pharmacology · 2019Article
- Targeting proteasome-associated deubiquitinases as a novel strategy for the treatment of estrogen receptor-positive breast cancer.Oncogenesis · 2018Article
- Discovering proteasomal deubiquitinating enzyme inhibitors for cancer therapy: lessons from rational design, nature and old drug reposition.Future medicinal chemistry · 2018Review
- Targeting the ubiquitin-proteasome system for cancer treatment: discovering novel inhibitors from nature and drug repurposing.Cancer metastasis reviews · 2017Article
- Metal-based proteasomal deubiquitinase inhibitors as potential anticancer agents.Cancer metastasis reviews · 2017Review
- A novel deubiquitinase inhibitor b-AP15 triggers apoptosis in both androgen receptor-dependent and -independent prostate cancers.Oncotarget · 2017Article
- Platinum pyrithione induces apoptosis in chronic myeloid leukemia cells resistant to imatinib via DUB inhibition-dependent caspase activation and Bcr-Abl downregulation.Cell death & disease · 2017Article
- Platinum-containing compound platinum pyrithione suppresses ovarian tumor proliferation through proteasome inhibition.Journal of experimental & clinical cancer research : CR · 2017Article
- Bilirubin neurotoxicity is associated with proteasome inhibition.Cell death & disease · 2017Article
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 2 countries.
Funding
Abstract
DNA is the well-known molecular target of current platinum-based anticancer drugs; consequently, their clinical use is severely restricted by their systemic toxicities and drug resistance originating from non-selective DNA damage. Various strategies have been developed to circumvent the shortcomings of platinum-based chemotherapy but the inherent problem remains unsolved. Here we report that platinum pyrithione (PtPT), a chemically well-characterized synthetic complex of platinum, inhibits proteasome function and thereby exhibits greater and more selective cytotoxicity to multiple cancer cells than cisplatin, without showing discernible DNA damage both in vitro and in vivo. Moreover, unlike the classical proteasome inhibitor bortezomib/Velcade which inhibits the proteasome via blocking the peptidase activity of 20S proteasomes, PtPT primarily deactivates 26S proteasome-associated deubiquitinases USP14 and UCHL5. Furthermore, PtPT can selectively induce cytotoxicity and proteasome inhibition in cancer cells from leukemia patients but not peripheral blood mononuclear cells from healthy humans. In nude mice, PtPT also remarkably inhibited tumor xenograft growth, without showing the adverse effects that were induced by cisplatin. Hence, we have discovered a new platinum-based anti-tumor agent PtPT which targets 26S proteasome-associated deubiquitinases rather than DNA in the cell and thereby exerts safer and more potent anti-tumor effects, identifying a highly translatable new platinum-based anti-cancer strategy.
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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.