ArticleBlood2012
Unique dual targeting of thymidylate synthase and topoisomerase1 by FdUMP[10] results in high efficacy against AML and low toxicity.
Article in Blood, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03741829 (TS Overexpression in SCLC), which is not on this map. Cited by 43 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.
TS Overexpression in SCLC: Mechanism and Therapeutic Targeting
Who cites it
43 citing papers in PubMed, 46 citations in OpenAlex.
- Activation of an adaptive antitumor immune response by the polymeric fluoropyrimidine CF10 involves TS/Top1 dual targeting.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Article
- CF10 Displays Improved Synergy with Oxaliplatin inCancers · 2026Article
- The fluoropyrimidine polymer CF10 synergizes with 5-ethynyl-2'-deoxyuridine by promoting telomere attrition and mitotic catastrophe.NAR molecular medicine · 2026Article
- Colorectal Cancer: Differential Gene Expression and In Vitro Response to 5-Fluorouracil, Novel Fluoropyrimidine F10, and Potential Synergy with Lupeol.International journal of molecular sciences · 2025Article
- Chemotherapeutic Spherical Nucleic Acids.ACS nano · 2025Article
- CF10 Displayed Improved Activity Relative to 5-FU in a Mouse CRLM Model Under Conditions of Physiological Folate.Cancers · 2025Article
- The polymeric fluoropyrimidine CF10 overcomes limitations of 5-FU in pancreatic ductal adenocarcinoma cells through increased replication stress.Cancer biology & therapy · 2024Article
- A minimalist multifunctional nano-prodrug for drug resistance reverse and integration with PD-L1 mAb for enhanced immunotherapy of hepatocellular carcinoma.Journal of nanobiotechnology · 2024Article
- Article
- Review
- Oligonucleotides Carrying Nucleoside Antimetabolites as Potential Prodrugs.Current medicinal chemistry · 2023Review
- Review of 5-FU resistance mechanisms in colorectal cancer: clinical significance of attenuated on-target effects.Cancer drug resistance (Alhambra, Calif.) · 2023Review
- A narrative review of genetic factors affecting fluoropyrimidine toxicity.Precision cancer medicine · 2021Article
- Inhibition of Human Uracil DNA Glycosylase Sensitizes a Large Fraction of Colorectal Cancer Cells to 5-Fluorodeoxyuridine and Raltitrexed but Not Fluorouracil.Molecular pharmacology · 2021Article
- AraC-FdUMP[10] Is a Next-Generation Fluoropyrimidine with Potent Antitumor Activity in PDAC and Synergy withMolecular cancer research : MCR · 2021Article
- Improved Antitumor Activity of the Fluoropyrimidine Polymer CF10 in Preclinical Colorectal Cancer Models through Distinct Mechanistic and Pharmacologic Properties.Molecular cancer therapeutics · 2021Article
- Chemistry of Fluorinated Pyrimidines in the Era of Personalized Medicine.Molecules (Basel, Switzerland) · 2020Review
- The Novel Phospholipid Mimetic KPC34 Is Highly Active Against Acute Myeloid Leukemia with Activated Protein Kinase C.Translational oncology · 2020Article
- Fluoropyrimidine Modulation of the Anti-Tumor Immune Response-Prospects for Improved Colorectal Cancer Treatment.Cancers · 2020Review
- Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Acute myeloid leukemia (AML) is an aggressive malignancy that leads to marrow failure and death. There is a desperate need for new therapies. The novel fluoropyrimidine, FdUMP[10], was highly active against both human AML cell lines, (IC(50) values, 3.4nM-21.5nM) and murine lines (IC(50) values, 123.8pM-131.4pM). In all cases, the IC(50) of FdUMP[10] was lower than for cytarabine and ∼ 1000 times lower than 5-fluorouracil (5-FU). FdUMP[10] remained effective against cells expressing the Flt3 internal tandem duplication, BCR-ABL, MN1, and an shRNA against p53. It had activity against patient samples at concentrations that did not affect normal hematopoietic cells. FdUMP[10] inhibited thymidylate synthase (TS) and trapped topoisomerase I cleavage complexes (Top1CCs), leading to DNA damage and apoptosis. All cell lines and nearly all primary AML samples examined expressed both TS and Top1. In vivo, FdUMP[10] was active against a syngeneic AML model with a survival advantage equivalent to doxorubicin plus cytarabine. 5-FU treatment was toxic and did not improve survival. FdUMP[10] was better tolerated than 5-FU or cytarabine plus doxorubicin and did not affect normal HSCs, while 5-FU dramatically impaired their ability to engraft. In summary, FdUMP[10] was highly efficacious and better tolerated than standard therapies.
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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.