ArticleMolecular pharmacology2010
Efficient hypoxic activation of the anticancer agent AQ4N by CYP2S1 and CYP2W1.
Article in Molecular pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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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
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 116 citations in OpenAlex.
- Targeting Hypoxia: Hypoxia-Activated Prodrugs in Cancer Therapy.Frontiers in oncology · 2021Pooled it
- CYP2W1 is highly expressed in adrenal glands and is positively associated with the response to mitotane in adrenocortical carcinoma.PloS one · 2014Trial
- Fluorinated Hypoxia-Responsive Aza-BODIPY for NIR-II FL/Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Orphan Cytochromes P450 as Possible Pharmacological Targets or Biomarkers in Breast Cancer.Current issues in molecular biology · 2025Review
- Strategy-Level Prodrug Synthesis.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Review
- Roles of Individual Human Cytochrome P450 Enzymes in Drug Metabolism.Pharmacological reviews · 2024Review
- Repurposing antifungal drugs for cancer therapy.Journal of advanced research · 2023Review
- Targeting DNA topoisomerase IIα (TOP2A) in the hypoxic tumour microenvironment using unidirectional hypoxia-activated prodrugs (uHAPs).IUBMB life · 2023Review
- CYP2S1 and CYP2W1 expression is associated with patient survival in breast cancer.The journal of pathology. Clinical research · 2022Article
- Hypoxia signaling: Challenges and opportunities for cancer therapy.Seminars in cancer biology · 2022Review
- Enhancing the therapeutic efficacy of nanoparticles for cancer treatment using versatile targeted strategies.Journal of hematology & oncology · 2022Review
- In vitro radiosensitization of breast cancer with hypoxia-activated prodrugs.Journal of cellular and molecular medicine · 2022Article
- Functional expression and regulation of eukaryotic cytochrome P450 enzymes in surrogate microbial cell factories.Engineering microbiology · 2022Review
- Targeted contrast agents and activatable probes for photoacoustic imaging of cancer.Chemical Society reviews · 2022Review
- Cytochrome P450 Binding and Bioactivation of Tumor-Targeted Duocarmycin Agents.Drug metabolism and disposition: the biological fate of chemicals · 2022Article
- Human Orphan Cytochromes P450: An Update.Current drug metabolism · 2022Article
- Cytochrome P450 isoforms 1A1, 1B1 AND 2W1 as targets for therapeutic intervention in head and neck cancer.Scientific reports · 2021Article
- EnamineACS central science · 2021Article
- Hypoxia-activated probe for NIR fluorescence and photoacoustic dual-mode tumor imaging.iScience · 2021Article
- Extrahepatic cytochrome P450 epoxygenases: pathophysiology and clinical significance in human gastrointestinal cancers.Oncotarget · 2021Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
AQ4N [1,4-bis{[2-(dimethylamino-N-oxide)ethyl]amino}-5,8-dihydroxyanthracene-9,10-dione], a prodrug with two dimethylamino N-oxide groups, is converted to the topoisomerase II inhibitor AQ4 [1,4-bis{[2-(dimethylamino)ethyl]amino}-5,8-dihydroxy-anthracene-9,10-dione] by reduction of the N-oxides to dimethylamino substituents. Earlier studies showed that several drug-metabolizing cytochrome P450 (P450) enzymes can catalyze this reductive reaction under hypoxic conditions comparable with those in solid tumors. CYP2S1 and CYP2W1, two extrahepatic P450 enzymes identified from the human genome whose functions are unknown, are expressed in hypoxic tumor cells at much higher levels than in normal tissue. Here, we demonstrate that CYP2S1, contrary to a published report (Mol Pharmacol 76:1031-1043, 2009), is efficiently reduced by NADPH-P450 reductase. Most importantly, both CYP2S1 and CYP2W1 are better catalysts for the reductive activation of AQ4N to AQ4 than all previously examined P450 enzymes. The overexpression of CYP2S1 and CYP2W1 in tumor tissues, together with their high catalytic activities for AQ4N activation, suggests that they may be exploited for the localized activation of anticancer prodrugs.
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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.