ArticleThe Biochemical journal2013
Small-molecule inhibition of MLL activity by disruption of its interaction with WDR5.
Article in The Biochemical journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
What it found
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The trial behind it
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Who cites it
85 citing papers in PubMed.
- Promiscuous RNA binding by WDR5 remodels the KMT2A (MLL1) histone methyltransferase complex to an inactive state.Molecular cell · 2026Article
- Recent advances of dual PROTACs for potential therapeutic applications.Molecular diversity · 2026Review
- Self-Dimerization Induced Proximity Targeting Chimeras (SDIPTAC) Lead to DCAF1 Loss of Function and Inhibition of HIV Replication.Journal of medicinal chemistry · 2026Article
- Promiscuous RNA binding by WDR5 remodels the KMT2A (MLL1) histone methyltransferase complex to an inactive state.bioRxiv : the preprint server for biology · 2026Article
- COMPASS-mediated epigenetic regulation of transcription accelerates forgetting with age.Research square · 2026Article
- Massive barcode-free chemical screenings enable the discovery of bioactive macrocycles with passive membrane permeability.Nature communications · 2026Article
- Chromatin Regulatory Targets for Anticancer Therapeutics.Chemical reviews · 2025Review
- A Target Class Ligandability Evaluation of WD40 Repeat-Containing Proteins.Journal of medicinal chemistry · 2025Article
- Crystal structures of DCAF1-PROTAC-WDR5 ternary complexes provide insight into DCAF1 substrate specificity.Nature communications · 2024Article
- WDR5 Binding to Histone Serotonylation Is Driven by an Edge-Face Aromatic Interaction with Unexpected Electrostatic Effects.Journal of the American Chemical Society · 2024Article
- Quantitative Hydrogen-Deuterium Exchange Mass Spectrometry for Simultaneous Structural Characterization and Affinity Indexing of Single Target Drug Candidate Libraries.Analytical chemistry · 2024Article
- The Wdr5-H3K4me3 Epigenetic Axis Regulates Pancreatic Tumor Immunogenicity and Immune Suppression.International journal of molecular sciences · 2024Article
- Article
- Epigenetic and transcriptional regulation of cytokine production by Plasmodium falciparum-exposed monocytes.Scientific reports · 2024Article
- Overlapping characteristics of weak interactions of two transcriptional regulators with WDR5.International journal of biological macromolecules · 2024Article
- Ribosome subunit attrition and activation of the p53-MDM4 axis dominate the response of MLL-rearranged cancer cells to WDR5 WIN site inhibition.bioRxiv : the preprint server for biology · 2024Article
- WD Repeat Domain 5 Inhibitors for Cancer Therapy: Not What You Think.Journal of clinical medicine · 2024Review
- Reepithelialization of Diabetic Skin and Mucosal Wounds Is Rescued by Treatment With Epigenetic Inhibitors.Diabetes · 2024Article
- Structure-Based Discovery of Potent, Orally Bioavailable Benzoxazepinone-Based WD Repeat Domain 5 Inhibitors.Journal of medicinal chemistry · 2023Article
- Discovery of Potent and Selective WDR5 Proteolysis Targeting Chimeras as Potential Therapeutics for Pancreatic Cancer.Journal of medicinal chemistry · 2023Article
25 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
22 authors.
Funding
Abstract
WDR5 (WD40 repeat protein 5) is an essential component of the human trithorax-like family of SET1 [Su(var)3-9 enhancer-of-zeste trithorax 1] methyltransferase complexes that carry out trimethylation of histone 3 Lys4 (H3K4me3), play key roles in development and are abnormally expressed in many cancers. In the present study, we show that the interaction between WDR5 and peptides from the catalytic domain of MLL (mixed-lineage leukaemia protein) (KMT2) can be antagonized with a small molecule. Structural and biophysical analysis show that this antagonist binds in the WDR5 peptide-binding pocket with a Kd of 450 nM and inhibits the catalytic activity of the MLL core complex in vitro. The degree of inhibition was enhanced at lower protein concentrations consistent with a role for WDR5 in directly stabilizing the MLL multiprotein complex. Our data demonstrate inhibition of an important protein-protein interaction and form the basis for further development of inhibitors of WDR5-dependent enzymes implicated in MLL-rearranged leukaemias or other 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.