ArticleNature protocols2016
Design, synthesis and evaluation of molecularly targeted hypoxia-activated prodrugs.
Article in Nature protocols, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
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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
39 citing papers in PubMed.
- Hypoxia-responsive supramolecular systems based on macrocycles and self-assembly structures.Medical gas research · 2027Review
- Coupling photodynamic hypoxia amplification with a self-reporting chemiluminescent prodrug for adaptive precision therapy.Materials today. Bio · 2026Article
- Article
- High-Affinity Peptide-Drug Conjugate Ligands for the TRIM24 PHD and Bromodomain.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Hypoxia Imaging as a Radiomics Signature in Tumors Using NovelbioRxiv : the preprint server for biology · 2025Article
- Indolequinone-Based Hypoxia-Activated Proteolysis Targeting Chimeras Selectively Degrade BRD4 in Hypoxic Cancer Cells.Journal of the American Chemical Society · 2025Article
- Hypoxia-activated fluorescent probes as markers of oxygen levels in plant cells and tissues.The New phytologist · 2025Article
- Targeting Tumor-Associated Hypoxia with Bioreductively Activatable Prodrug Conjugates Derived from Dihydronaphthalene, Benzosuberene, and Indole-based Inhibitors of Tubulin Polymerization.RSC medicinal chemistry · 2025Article
- Binuclear Lanthanide Complexes as Magnetic Resonance and Optical Imaging Probes for Redox Sensing.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Fluorescent Molecular Probe for Imaging Hypoxia in 2D Cell Culture Monolayers and 3D Tumor Spheroids: The Cell Membrane Partition Model for Predicting Probe Distribution in a Spheroid.ACS applied materials & interfaces · 2025Article
- Dual-Action-Only PROTACs.Journal of the American Chemical Society · 2025Article
- Imaging hypoxia for head and neck cancer: current status, challenges, and prospects.Theranostics · 2025Review
- Phenotypic-Based Discovery and Exploration of a Resorufin Scaffold with Activity against Mycobacterium tuberculosis.ChemMedChem · 2024Article
- Novel Prodrug Strategies for the Treatment of Tuberculosis.Chemistry, an Asian journal · 2024Review
- Hypoxia-Responsive Prodrug of ATR Inhibitor, AZD6738, Selectively Eradicates Treatment-Resistant Cancer Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Article
- Hypoxia-activated prodrugs of phenolic olaparib analogues for tumour-selective chemosensitisation.RSC medicinal chemistry · 2023Article
- Two Color Imaging of Different Hypoxia Levels in Cancer Cells.Journal of the American Chemical Society · 2023Article
- A hypoxia-activated NO donor for the treatment of myocardial hypoxia injury.Chemical science · 2022Article
- The importance of hypoxia in radiotherapy for the immune response, metastatic potential and FLASH-RT.International journal of radiation biology · 2022Review
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Regions of insufficient oxygen supply-hypoxia-occur in diverse contexts across biology in both healthy and diseased organisms. The difference in the chemical environment between a hypoxic biological system and one with normal oxygen levels provides an opportunity for targeting compound delivery to hypoxic regions by using bioreductive prodrugs. Here we detail a protocol for the efficient synthesis of (1-methyl-2-nitro-1H-imidazol-5-yl)methanol, which is a key intermediate that can be converted into a range of 1-methyl-2-nitro-1H-imidazole-based precursors of bioreductive prodrugs. We outline methods for attaching the bioreductive group to a range of functionalities, and we discuss the strategy for positioning of the group on the biologically active parent compound. We have used two parent checkpoint kinase 1 (Chk1) inhibitors to exemplify the protocol. The PROCEDURE also describes a suite of reduction assays, of increasing biological relevance, to validate the bioreductive prodrug. These assays are applied to an exemplar compound, CH-01, which is a bioreductive Chk1 inhibitor. This protocol has broad applications to the development of hypoxia-targeted compounds.
Indexed as
Identifiers
27010756What 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.