ArticleACS chemical biology2014
Competitive binding of a benzimidazole to the histone-binding pocket of the Pygo PHD finger.
Article in ACS chemical biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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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
31 citing papers in PubMed, 64 citations in OpenAlex.
- The upregulation of GDF15 is controlled epigenetically by oncogenic TCF19 signaling in human hepatocellular carcinoma.iScience · 2025Article
- Identifying ligands for the PHD1 finger of KDM5A through high-throughput screening.RSC chemical biology · 2024Article
- The Wnt-dependent and Wnt-independent functions of BCL9 in development, tumorigenesis, and immunity: Implications in therapeutic opportunities.Genes & diseases · 2024Review
- Deciphering the dual roles of PHD finger proteins from oncogenic drivers to tumor suppressors.Frontiers in cell and developmental biology · 2024Review
- Fragment-Based NMR Screening of the BPTF PHD Finger Methyl Lysine Reader Leads to the First Small-Molecule Inhibitors.ACS medicinal chemistry letters · 2023Article
- Drug Discovery Targeting Nuclear Receptor Binding SET Domain Protein 2 (NSD2).Journal of medicinal chemistry · 2023Review
- Cyclic peptides target the aromatic cage of a PHD-finger reader domain to modulate epigenetic protein function.Chemical science · 2023Article
- Non-histone binding functions of PHD fingers.Trends in biochemical sciences · 2023Review
- Chemical tools targeting readers of lysine methylation.Current opinion in chemical biology · 2023Review
- Reading and erasing of the phosphonium analogue of trimethyllysine by epigenetic proteins.Communications chemistry · 2022Article
- Covalent labeling of a chromatin reader domain using proximity-reactive cyclic peptides.Chemical science · 2022Article
- Discovery and Mechanism of Small Molecule Inhibitors Selective for the Chromatin-Binding Domains of Oncogenic UHRF1.Biochemistry · 2022Article
- Targeting Epigenetic Regulatory Enzymes for Cancer Therapeutics: Novel Small-Molecule Epidrug Development.Frontiers in oncology · 2022Review
- Targeting TRIM Proteins: A Quest towards Drugging an Emerging Protein Class.Chembiochem : a European journal of chemical biology · 2021Review
- The WNT/β-catenin dependent transcription: A tissue-specific business.WIREs mechanisms of disease · 2021Review
- The structural biology of canonical Wnt signalling.Biochemical Society transactions · 2020Review
- Targeting epigenetic protein-protein interactions with small-molecule inhibitors.Future medicinal chemistry · 2020Review
- Small Molecules Targeting the Specific Domains of Histone-Mark Readers in Cancer Therapy.Molecules (Basel, Switzerland) · 2020Review
- Article
- Targeting non-bromodomain chromatin readers.Nature structural & molecular biology · 2019Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The Pygo-BCL9 complex is a chromatin reader, facilitating β-catenin-mediated oncogenesis, and is thus emerging as a potential therapeutic target for cancer. Its function relies on two ligand-binding surfaces of Pygo's PHD finger that anchor the histone H3 tail methylated at lysine 4 (H3K4me) with assistance from the BCL9 HD1 domain. Here, we report the first use of fragment-based screening by NMR to identify small molecules that block protein-protein interactions by a PHD finger. This led to the discovery of a set of benzothiazoles that bind to a cleft emanating from the PHD-HD1 interface, as defined by X-ray crystallography. Furthermore, we discovered a benzimidazole that docks into the H3K4me specificity pocket and displaces the native H3K4me peptide from the PHD finger. Our study demonstrates the ligandability of the Pygo-BCL9 complex and uncovers a privileged scaffold as a template for future development of lead inhibitors of oncogenesis.
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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.