ArticleCommunications chemistry2022
A platinum(IV) prodrug strategy to overcome glutathione-based oxaliplatin resistance.
Article in Communications chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 50 citations in OpenAlex.
- Functionalized biomaterial platforms for interventional embolization therapy of hepatocellular carcinoma.Bioactive materials · 2027Review
- Liposomal Formulation of a Tetravalent Oxaliplatin Prodrug: Preparation and Antitumor Efficacy.Pharmaceutical research · 2026Article
- Chemotherapeutic Potential of Fluorouracil-Platinum (IV) Prodrugs Against Cisplatin-Resistant Colorectal Cancer Cells.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Article
- A Multiple Enzyme-Mimetic Platinum-Ruthenium Nanohybrid Prodrug Potentiates Chemo-/Chemodynamic-/Immuno-Therapy of Hypoxic Tumors.Advanced healthcare materials · 2026Article
- Improved Systemic Immunochemotherapy Employing an Oxaliplatin-TLR7/8 Agonist Prodrug Strategy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Multifunctional Nano Immunostimulant: Overcoming Immunosuppressive Microenvironment for Antitumor Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Dual acting oxaliplatin (IV) prodrug loaded albumin nanoparticles for safer synergistic anticancer action against triple negative breast cancer.Drug delivery and translational research · 2025Article
- Targeting the crosstalk of metabolism reprogramming and replication stress: novel strategy to combat cancer.Medical oncology (Northwood, London, England) · 2025Review
- Research Progress of Platinum-Based Complexes in Lung Cancer Treatment: Mechanisms, Applications, and Challenges.International journal of molecular sciences · 2025Review
- Article
- Personalized drug stratification using endoscopic samples to assess ex vivo gastric cancer tissue susceptibility to chemotherapy and immune checkpoint inhibitors.Clinical and experimental medicine · 2025Article
- Multi-Pathway Study for Oxaliplatin Resistance Reduction.Current issues in molecular biology · 2025Review
- Exploring the Structure-Activity Relationships of Albumin-Targeted Picoplatin-Based Platinum(IV) Prodrugs.Inorganic chemistry · 2025Article
- AKR1C1 interacts with STAT3 to increase intracellular glutathione and confers resistance to oxaliplatin in colorectal cancer.Acta pharmaceutica Sinica. B · 2024Article
- Chemotherapeutic Potential of Chlorambucil-Platinum(IV) Prodrugs against Cisplatin-Resistant Colorectal Cancer Cells.International journal of molecular sciences · 2024Article
- Anticancer Effect of PtCancers · 2024Article
- Stepwise optimization of tumor-targeted dual-action platinum(iv)-gemcitabine prodrugs.Inorganic chemistry frontiers · 2024Article
- Research Progress of Disulfide Bond Based Tumor Microenvironment Targeted Drug Delivery System.International journal of nanomedicine · 2024Review
- Platinum(IV)-Gold(I) Agents with Promising Anticancer Activity: Selected Studies in 2D and 3D Triple-Negative Breast Cancer Models.Chemistry (Weinheim an der Bergstrasse, Germany) · 2023Article
- Tumor-targeted dual-action NSAID-platinum(iv) anticancer prodrugs.Inorganic chemistry frontiers · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Clinical efficacy of oxaliplatin is frequently limited by severe adverse effects and therapy resistance. Acquired insensitivity to oxaliplatin is, at least in part, associated with elevated levels of glutathione (GSH). In this study we report on an oxaliplatin-based platinum(IV) prodrug, which releases L-buthionine-S,R-sulfoximine (BSO), an inhibitor of glutamate-cysteine ligase, the rate-limiting enzyme in GSH biosynthesis. Two complexes bearing either acetate (BSO-OxOAc) or an albumin-binding maleimide (BSO-OxMal) as second axial ligand were synthesized and characterized. The in vitro anticancer activity of BSO-OxOAc was massively reduced in comparison to oxaliplatin, proving its prodrug nature. Nevertheless, the markedly lower intracellular oxaliplatin uptake in resistant HCT116/OxR cells was widely overcome by BSO-OxOAc resulting in distinctly reduced resistance levels. Platinum accumulation in organs of a colorectal cancer mouse model revealed higher tumor selectivity of BSO-OxMal as compared to oxaliplatin. This corresponded with increased antitumor activity, resulting in significantly enhanced overall survival. BSO-OxMal-treated tumors exhibited reduced GSH levels, proliferative activity and enhanced DNA damage (pH2AX) compared to oxaliplatin. Conversely, pH2AX staining especially in kidney cells was distinctly increased by oxaliplatin but not by BSO-OxMal. Taken together, our data provide compelling evidence for enhanced tumor specificity of the oxaliplatin(IV)/BSO prodrug.
Identifiers
What OpenQuestion holds
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.