ArticleACS chemical biology2016
Small Molecule Microarrays Enable the Identification of a Selective, Quadruplex-Binding Inhibitor of MYC Expression.
Article in ACS chemical biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
62 citing papers in PubMed, 125 citations in OpenAlex.
- Chemically modified CRISPR-Cas9 enables targeting of individual G-quadruplex and i-motif structures, revealing ligand-dependent transcriptional perturbation.Nature communications · 2025Article
- A Small Molecule Selectively Targets N-Myc to Suppress Neuroblastoma Cancer Progression.International journal of biological sciences · 2025Article
- A Phenotypic Approach to the Discovery of Potent G-Quadruplex Targeted Drugs.Molecules (Basel, Switzerland) · 2024Review
- Targeting specific DNA G-quadruplexes with CRISPR-guided G-quadruplex-binding proteins and ligands.Nature cell biology · 2024Article
- G-quadruplex-guided cisplatin triggers multiple pathways in targeted chemotherapy and immunotherapy.Chemical science · 2024Article
- Research Progress on Pyroptosis in Hematological Malignancies.Current treatment options in oncology · 2023Review
- Hepatitis B Virus Epsilon (ε) RNA Element: Dynamic Regulator of Viral Replication and Attractive Therapeutic Target.Viruses · 2023Review
- G-Quadruplexes in c-MYC Promoter as Targets for Cancer Therapy.Biomedicines · 2023Review
- DNA G-quadruplex-stabilizing metal complexes as anticancer drugs.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2023Review
- The Intertwined Role of 8-oxodG and G4 in Transcription Regulation.International journal of molecular sciences · 2023Review
- A Functional Screening Identifies a New Organic Selenium Compound Targeting Cancer Stem Cells: Role of c-Myc Transcription Activity Inhibition in Liver Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Affinity Chromatography-Based Assays for the Screening of Potential Ligands Selective for G-Quadruplex Structures.ChemistryOpen · 2022Article
- Methodological advances of bioanalysis and biochemical targeting of intracellular G-quadruplexes.Exploration (Beijing, China) · 2022Review
- Review
- Designing strategies of small-molecule compounds for modulating non-coding RNAs in cancer therapy.Journal of hematology & oncology · 2022Review
- Screening of Minimalist Noncanonical Sites in Duplex DNA and RNA Reveals Context and Motif-Selective Binding by Fluorogenic Base Probes.Chemistry (Weinheim an der Bergstrasse, Germany) · 2022Article
- The MYC oncogene - the grand orchestrator of cancer growth and immune evasion.Nature reviews. Clinical oncology · 2022Review
- Structural insights of the conserved "priming loop" of hepatitis B virus pre-genomic RNA.Journal of biomolecular structure & dynamics · 2022Article
- Selective Recognition of a Single HIV-1 G-Quadruplex by Ultrafast Small-Molecule Screening.Analytical chemistry · 2021Article
- Targeted Downregulation of MYC through G-quadruplex Stabilization by DNAi.Molecules (Basel, Switzerland) · 2021Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
The transcription factor MYC plays a pivotal role in cancer initiation, progression, and maintenance. However, it has proven difficult to develop small molecule inhibitors of MYC. One attractive route to pharmacological inhibition of MYC has been the prevention of its expression through small molecule-mediated stabilization of the G-quadruplex (G4) present in its promoter. Although molecules that bind globally to quadruplex DNA and influence gene expression are well-known, the identification of new chemical scaffolds that selectively modulate G4-driven genes remains a challenge. Here, we report an approach for the identification of G4-binding small molecules using small molecule microarrays (SMMs). We use the SMM screening platform to identify a novel G4-binding small molecule that inhibits MYC expression in cell models, with minimal impact on the expression of other G4-associated genes. Surface plasmon resonance (SPR) and thermal melt assays demonstrated that this molecule binds reversibly to the MYC G4 with single digit micromolar affinity, and with weaker or no measurable binding to other G4s. Biochemical and cell-based assays demonstrated that the compound effectively silenced MYC transcription and translation via a G4-dependent mechanism of action. The compound induced G1 arrest and was selectively toxic to MYC-driven cancer cell lines containing the G4 in the promoter but had minimal effects in peripheral blood mononucleocytes or a cell line lacking the G4 in its MYC promoter. As a measure of selectivity, gene expression analysis and qPCR experiments demonstrated that MYC and several MYC target genes were downregulated upon treatment with this compound, while the expression of several other G4-driven genes was not affected. In addition to providing a novel chemical scaffold that modulates MYC expression through G4 binding, this work suggests that the SMM screening approach may be broadly useful as an approach for the identification of new G4-binding small molecules.
Indexed as
Identifiers
What 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.