ArticleJournal of medicinal chemistry2016
A Novel Tumor-Activated Prodrug Strategy Targeting Ferrous Iron Is Effective in Multiple Preclinical Cancer Models.
Article in Journal of medicinal chemistry, 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
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
20 citing papers in PubMed, 36 citations in OpenAlex.
- Toward Tumor-Conditional Release of Histone Deacetylase Inhibitors from Nongenotoxic Drug Conjugates.ACS medicinal chemistry letters · 2026Article
- Insights into Free Drug Release from EfficaciousACS chemical biology · 2025Article
- Targeting vascular senescence in cardiovascular disease with aging.The journal of cardiovascular aging · 2024Article
- Drug conjugates for the treatment of lung cancer: from drug discovery to clinical practice.Experimental hematology & oncology · 2024Review
- DMT1-dependent endosome-mitochondria interactions regulate mitochondrial iron translocation and metastatic outgrowth.Oncogene · 2024Article
- In vivo bioluminescence imaging of labile iron in xenograft models and liver using FeAL-1, an iron-activatable form of D-luciferin.Cell chemical biology · 2023Article
- Elevated labile iron in castration-resistant prostate cancer is targetable with ferrous iron-activatable antiandrogen therapy.European journal of medicinal chemistry · 2023Article
- 40 Years of Duocarmycins: A Graphical Structure/Function Review of Their Chemical Evolution, from SAR to Prodrugs and ADCs.JACS Au · 2022Review
- Multicomponent Direct Assembly ofThe Journal of organic chemistry · 2022Article
- Ferrous iron-activatable drug conjugate achieves potent MAPK blockade in KRAS-driven tumors.The Journal of experimental medicine · 2022Article
- Prostate cancer research in the 21st century; report from the 2021 Coffey-Holden prostate cancer academy meeting.The Prostate · 2022Review
- Antibody-drug conjugates: Recent advances in linker chemistry.Acta pharmaceutica Sinica. B · 2021Review
- Ferronostics: Measuring Tumoral Ferrous Iron with PET to Predict Sensitivity to Iron-Targeted Cancer Therapies.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2021Article
- Ferrous Iron-Dependent Pharmacology.Trends in pharmacological sciences · 2021Review
- From Iron Chelation to Overload as a Therapeutic Strategy to Induce Ferroptosis in Leukemic Cells.Frontiers in oncology · 2020Review
- Altered Iron Metabolism and Impact in Cancer Biology, Metastasis, and Immunology.Frontiers in oncology · 2020Review
- Targeting Mobilization of Ferrous Iron inACS infectious diseases · 2019Article
- Measuring Dynamic Changes in the Labile Iron Pool in Vivo with a Reactivity-Based Probe for Positron Emission Tomography.ACS central science · 2019Article
- FINONature chemical biology · 2018Article
- In vivo bioluminescence imaging of labile iron accumulation in a murine model ofProceedings of the National Academy of Sciences of the United States of America · 2017Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Here we describe a new approach for tumor targeting in which augmented concentrations of Fe(II) in cancer cells and/or the tumor microenvironment triggers drug release from an Fe(II)-reactive prodrug conjugate. The 1,2,4-trioxolane scaffold developed to enable this approach can in principle be applied to a broad range of cancer therapeutics and is illustrated here with Fe(II)-targeted forms of a microtubule toxin and a duocarmycin-class DNA-alkylating agent. We show that the intrinsic reactivity/toxicity of the duocarmycin analog is masked in the conjugated form and this greatly reduced toxicity in mice. This in turn permitted elevated dosing levels, leading to higher systemic exposure and a significantly improved response in tumor xenograft models. Overall our results suggest that Fe(II)-dependent drug delivery via trioxolane conjugates could have significant utility in expanding the therapeutic index of a range of clinical and preclinical stage cancer chemotherapeutics.
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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.