ArticleCancer research2020
Bromodomain-Selective BET Inhibitors Are Potent Antitumor Agents against MYC-Driven Pediatric Cancer.
Article in Cancer research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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
26 citing papers in PubMed, 41 citations in OpenAlex.
- Eyes Toward the Clinic: Selective Inhibition and Degradation Approaches to Bromodomain-Containing Proteins.Chembiochem : a European journal of chemical biology · 2026Review
- A Conserved Enhancer Locus in Extrachromosomal DNA and Homogeneously Staining Regions Activates MYC Transcription in Group 3 Medulloblastoma.Cancer research · 2026Article
- Choline metabolism drives metastasis in BRCA1-deficient ovarian cancers by activating FAM3C.Nature communications · 2026Article
- MYC Addiction as a Targetable Vulnerability in Nelarabine-Resistant T-Cell Acute Lymphoblastic Leukemia.Cancer science · 2026Article
- Bromodomain-Driven Regulation of Stem Cells: A Potential Target for Cancer Therapeutic Intervention.Stem cell reviews and reports · 2026Review
- Positional isomers of Indolyl-benzodiazepines display dissimilar binding and recruitment of BET transcriptional regulators to targeted genomic loci.Bioorganic chemistry · 2025Article
- Epigenetic Dysregulation in Cancer: Implications for Gene Expression and DNA Repair-Associated Pathways.International journal of molecular sciences · 2025Review
- Transcription factor 4 is a key mediator of oncogenesis in neuroblastoma by promoting MYC activity.Molecular oncology · 2025Article
- Group 3 medulloblastoma transcriptional networks collapse under domain specific EP300/CBP inhibition.Nature communications · 2024Article
- BRD4 isoforms have distinct roles in tumour progression and metastasis in rhabdomyosarcoma.EMBO reports · 2024Article
- Bromodomain and extraterminal (BET) proteins: biological functions, diseases, and targeted therapy.Signal transduction and targeted therapy · 2023Review
- Domain-Selective BET Ligands Yield Next-Generation Synthetic Genome Readers/Regulators with Nonidentical Cellular Functions.Journal of the American Chemical Society · 2023Article
- Bromodomain inhibitors and therapeutic applications.Current opinion in chemical biology · 2023Review
- Streamlined DNA-encoded small molecule library screening and validation for the discovery of novel chemotypes targeting BET proteins.Molecular therapy. Nucleic acids · 2023Article
- Targeting bromodomain-containing proteins: research advances of drug discovery.Molecular biomedicine · 2023Review
- BET Bromodomain Inhibitors: Novel Design Strategies and Therapeutic Applications.Molecules (Basel, Switzerland) · 2023Review
- Novel forms of prostate cancer chemoresistance to successful androgen deprivation therapy demand new approaches: Rationale for targeting BET proteins.The Prostate · 2022Review
- Discovery of potent BET bromodomain 1 stereoselective inhibitors using DNA-encoded chemical library selections.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Targeting bromodomain and extra-terminal proteins to inhibit neuroblastoma tumorigenesis through regulating MYCN.Frontiers in cell and developmental biology · 2022Review
- Targeting Oncogenic Transcriptional Networks in Neuroblastoma: From N-Myc to Epigenetic Drugs.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
30 authors at 1 institution in 1 country.
Funding
Abstract
Inhibition of members of the bromodomain and extraterminal (BET) family of proteins has proven a valid strategy for cancer chemotherapy. All BET identified to date contain two bromodomains (BD; BD1 and BD2) that are necessary for recognition of acetylated lysine residues in the N-terminal regions of histones. Chemical matter that targets BET (BETi) also interact via these domains. Molecular and cellular data indicate that BD1 and BD2 have different biological roles depending upon their cellular context, with BD2 particularly associated with cancer. We have therefore pursued the development of BD2-selective molecules both as chemical probes and as potential leads for drug development. Here we report the structure-based generation of a novel series of tetrahydroquinoline analogs that exhibit >50-fold selectivity for BD2 versus BD1. This selective targeting resulted in engagement with BD-containing proteins in cells, resulting in modulation of MYC proteins and downstream targets. These compounds were potent cytotoxins toward numerous pediatric cancer cell lines and were minimally toxic to nontumorigenic cells. In addition, unlike the pan BETi (+)-JQ1, these BD2-selective inhibitors demonstrated no rebound expression effects. Finally, we report a pharmacokinetic-optimized, metabolically stable derivative that induced growth delay in a neuroblastoma xenograft model with minimal toxicity. We conclude that BD2-selective agents are valid candidates for antitumor drug design for pediatric malignancies driven by the MYC oncogene. SIGNIFICANCE: This study presents bromodomain-selective BET inhibitors that act as antitumor agents and demonstrates that these molecules have
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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.