ArticleACS medicinal chemistry letters2016
Structure-Guided Discovery of Selective Antagonists for the Chromodomain of Polycomb Repressive Protein CBX7.
Article in ACS medicinal chemistry letters, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 71 citations in OpenAlex.
- ANRIL in Cardiovascular Diseases: Expression, Mechanism and Therapeutic Implications.Cardiovascular drugs and therapy · 2026Review
- Development of High-Affinity CHD1 Chromodomain Inhibitors.Journal of medicinal chemistry · 2026Article
- Structural landscape of H3K27me3 recognition by protein domains and their potential for inhibition.The Journal of biological chemistry · 2026Review
- Epigenetic reader chromodomain as a potential therapeutic target.RSC chemical biology · 2025Review
- Unravelling the impact of the chromobox proteins in human cancers.Cell death & disease · 2025Review
- Anticancer benzimidazole derivatives as inhibitors of epigenetic targets: a review article.RSC advances · 2025Review
- Pharmacological targeting of CBX7 alters the epigenetic landscape and induces differentiation of leukemic cells.Blood neoplasia · 2024Article
- Epigenetic regulation by polycomb repressive complex 1 promotes cerebral cavernous malformations.EMBO molecular medicine · 2024Article
- How CBX proteins regulate normal and leukemic blood cells.FEBS letters · 2024Review
- Chemical tools targeting readers of lysine methylation.Current opinion in chemical biology · 2023Review
- Chromobox proteins in cancer: Multifaceted functions and strategies for modulation (Review).International journal of oncology · 2023Review
- St18 specifies globus pallidus projection neuron identity in MGE lineage.Nature communications · 2022Article
- The role of long non-coding RNA ANRIL in the development of atherosclerosis.Non-coding RNA research · 2022Review
- Reprogramming CBX8-PRC1 function with a positive allosteric modulator.Cell chemical biology · 2022Article
- Systematic Variation of Both the Aromatic Cage and Dialkyllysine via GCE-SAR Reveal Mechanistic Insights in CBX5 Reader Protein Binding.Journal of medicinal chemistry · 2022Article
- Article
- Improved methods for targeting epigenetic reader domains of acetylated and methylated lysine.Current opinion in chemical biology · 2021Review
- A Potent, Selective CBX2 Chromodomain Ligand and Its Cellular Activity During Prostate Cancer Neuroendocrine Differentiation.Chembiochem : a European journal of chemical biology · 2021Article
- Mimicking the Nucleosomal Context in Peptide-Based Binders of a H3K36me Reader Increases Binding Affinity While Altering the Binding Mode.Molecules (Basel, Switzerland) · 2020Article
- Targeting epigenetic protein-protein interactions with small-molecule inhibitors.Future medicinal chemistry · 2020Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
The chromobox 7 (CBX7) protein of the polycomb repressive complex 1 (PRC1) functions to repress transcription of tumor suppressor p16 (INK4a) through long noncoding RNA, ANRIL (antisense noncoding RNA in the INK4 locus) directed chromodomain (ChD) binding to trimethylated lysine 27 of histone H3 (H3K27me3), resulting in chromatin compaction at the INK4a/ARF locus. In this study, we report structure-guided discovery of two distinct classes of small-molecule antagonists for the CBX7ChD. Our Class A compounds, a series including analogues of the previously reported MS452, inhibit CBX7ChD/methyl-lysine binding by occupying the H3K27me3 peptide binding site, whereas our Class B compound, the newly discovered MS351, appears to inhibit H3K27me3 binding when CBX7ChD is bound to RNA. Our crystal structure of the CBX7ChD/MS351 complex reveals the molecular details of ligand recognition by the aromatic cage residues that typically engage in methyl-lysine binding. We further demonstrate that MS351 effectively induces transcriptional derepression of CBX7 target genes, including p16 (INK4a) in mouse embryonic stem cells and human prostate cancer PC3 cells. Thus, MS351 represents a new class of ChD antagonists that selectively targets the biologically active form of CBX7 of the PRC1 in long noncoding RNA- and H3K27me3-directed gene transcriptional repression.
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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.