ArticleJournal of the American Chemical Society2014
Reprogramming the mechanism of action of chlorambucil by coupling to a G-quadruplex ligand.
Article in Journal of the American Chemical Society, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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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
24 citing papers in PubMed, 84 citations in OpenAlex.
- From alkylating to shape-shifting G-quadruplex ligands: the RHAU peptide story.Nucleic acids research · 2026Article
- Causal Effects of Plasma Metabolites on Leukemia: A Mendelian Randomization Study.Metabolites · 2025Article
- Mapping small molecule-RNA binding sites via Chem-CLIP synergized with capillary electrophoresis and nanopore sequencing.Nucleic acids research · 2025Article
- Transcriptome-Wide, Unbiased Profiling of Ribonuclease Targeting Chimeras.Journal of the American Chemical Society · 2024Article
- G-quadruplex-guided cisplatin triggers multiple pathways in targeted chemotherapy and immunotherapy.Chemical science · 2024Article
- Dual-responsive chondroitin sulfate self-assembling nanoparticles for combination therapy in metastatic cancer cells.International journal of pharmaceutics: X · 2024Article
- Therapeutic effect of F127-folate@PLGA/CHL/IR780 nanoparticles on folate receptor-expressing cancer cells.Beilstein journal of nanotechnology · 2024Article
- Pervasive transcriptome interactions of protein-targeted drugs.Nature chemistry · 2023Article
- Chlorambucil-Bearing Hybrid Molecules in the Development of Potential Anticancer Agents.Molecules (Basel, Switzerland) · 2023Review
- Genotoxicity of cytokines at chemotherapy-induced 'storm' concentrations in a model of the human bone marrow.Mutagenesis · 2023Article
- A red light-triggered chemical tool for sequence-specific alkylation of G-quadruplex and I-motif DNA.Nucleic acids research · 2023Article
- Potent Chlorambucil-Platinum(IV) Prodrugs.International journal of molecular sciences · 2022Article
- Article
- Visualization of ligand-induced c-MYC duplex-quadruplex transition and direct exploration of the altered c-MYC DNA-protein interactions in cells.Nucleic acids research · 2022Article
- Major Achievements in the Design of Quadruplex-Interactive Small Molecules.Pharmaceuticals (Basel, Switzerland) · 2022Review
- DNA folds threaten genetic stability and can be leveraged for chemotherapy.RSC chemical biology · 2021Review
- Reactive OFF-ON type alkylating agents for higher-ordered structures of nucleic acids.Nucleic acids research · 2019Article
- Developing Novel G-Quadruplex Ligands: from Interaction with Nucleic Acids to Interfering with Nucleic Acid⁻Protein Interaction.Molecules (Basel, Switzerland) · 2019Review
- Emerging treatment options for patients with p53-pathway-deficient CLL.Therapeutic advances in hematology · 2019Review
- Probing of G-Quadruplex Structures via Ligand-Sensitized Photochemical Reactions inScientific reports · 2018Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
The nitrogen mustard Chlorambucil (Chl) generates covalent adducts with double-helical DNA and inhibits cell proliferation. Among these adducts, interstrand cross-links (ICLs) are the most toxic, as they stall replication by generating DNA double strand breaks (DSBs). Conversely, intrastrand cross-links generated by Chl are efficiently repaired by a dedicated Nucleotide Excision Repair (NER) enzyme. We synthesized a novel cross-linking agent that combines Chl with the G-quadruplex (G4) ligand PDS (PDS-Chl). We demonstrated that PDS-Chl alkylates G4 structures at low μM concentrations, without reactivity toward double- or single-stranded DNA. Since intramolecular G4s arise from a single DNA strand, we reasoned that preferential alkylation of such structures might prevent the generation of ICLs, while favoring intrastrand cross-links. We observed that PDS-Chl selectively impairs growth in cells genetically deficient in NER, but did not show any sensitivity to the repair gene BRCA2, involved in double-stranded break repair. Our findings suggest that G4 targeting of this clinically important alkylating agent alters the overall mechanism of action. These insights may inspire new opportunities for intervention in diseases specifically characterized by genetic impairment of NER, such as skin and testicular cancers.
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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.