ArticleOncogene2022
Discovery of a dual WDR5 and Ikaros PROTAC degrader as an anti-cancer therapeutic.
Article in Oncogene, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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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.
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Who cites it
31 citing papers in PubMed, 53 citations in OpenAlex.
- Recent advances of dual PROTACs for potential therapeutic applications.Molecular diversity · 2026Review
- Eyes Toward the Clinic: Selective Inhibition and Degradation Approaches to Bromodomain-Containing Proteins.Chembiochem : a European journal of chemical biology · 2026Review
- Review
- Prospects and advances of PROTAC in the treatment of hematologic malignancies.Experimental hematology & oncology · 2026Review
- Mono-ubiquitination of histone H2A lysine 119 (H2AK119Ub): its multifaceted role in biology and implication in diseases.MedScience · 2026Review
- Contemporary Developments in PROTACs for Cancer Management: An In-Depth Review.Current topics in medicinal chemistry · 2026Review
- Insights into WDR5: unveiling its functions, regulation, and impact on skeletal muscle.Epigenetics · 2025Review
- Review
- Chromatin Regulatory Targets for Anticancer Therapeutics.Chemical reviews · 2025Review
- Therapeutic Targeting of Protein Lysine and Arginine Methyltransferases: Principles and Strategies for Inhibitor Design.International journal of molecular sciences · 2025Review
- Comparative outcome and prognostic factor analysis among MDS/AML patients with TP53 mutations, snps, and wild type.Human genomics · 2025Article
- Unbiased mapping of cereblon neosubstrate landscape by high-throughput proteomics.Nature communications · 2025Article
- Insights into KMT2A rearrangements in acute myeloid leukemia: from molecular characteristics to targeted therapies.Biomarker research · 2025Review
- Pharmacologic degradation of WDR5 suppresses oncogenic activities of SS18::SSX and provides a therapeutic of synovial sarcoma.Science advances · 2025Article
- Crystal structures of DCAF1-PROTAC-WDR5 ternary complexes provide insight into DCAF1 substrate specificity.Nature communications · 2024Article
- Histone methyltransferase KMT2A: Developmental regulation to oncogenic transformation.The Journal of biological chemistry · 2024Review
- The Wild West of spike-in normalization.Nature biotechnology · 2024Article
- Luciferase- and HaloTag-based reporter assays to measure small-molecule-induced degradation pathway in living cells.Nature protocols · 2024Review
- Initial Characterization of WDR5B Reveals a Role in the Proliferation of Retinal Pigment Epithelial Cells.Cells · 2024Article
- Article
Corrections and comments
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Authors and funding
19 authors at 5 institutions in 1 country.
Funding
Abstract
WD repeat domain 5 (WDR5), an integral component of the MLL/KMT2A lysine methyltransferase complex, is critically involved in oncogenesis and represents an attractive onco-target. Inhibitors targeting protein-protein interactions (PPIs) between WDR5 and its binding partners, however, do not inhibit all of WDR5-mediated oncogenic functions and exert rather limited antitumor effects. Here, we report a cereblon (CRBN)-recruiting proteolysis targeting chimera (PROTAC) of WDR5, MS40, which selectively degrades WDR5 and the well-established neo-substrates of immunomodulatory drugs (IMiDs):CRBN, the Ikaros zinc finger (IKZF) transcription factors IKZF1 and IKZF3. MS40-induced WDR5 degradation caused disassociation of the MLL/KMT2A complex off chromatin, resulting in decreased H3K4me2. Transcriptomic profiling revealed that targets of both WDR5 and IMiDs:CRBN were significantly repressed by treatment of MS40. In MLL-rearranged leukemias, which exhibit IKZF1 high expression and dependency, co-suppression of WDR5 and Ikaros by MS40 is superior in suppressing oncogenesis to the WDR5 PPI inhibitor, to MS40's non-PROTAC analog controls (MS40N1 and MS40N2, which do not bind CRBN and WDR5, respectively), and to a matched VHL-based WDR5 PROTAC (MS169, which degrades WDR5 but not Ikaros). MS40 suppressed the growth of primary leukemia patient cells in vitro and patient-derived xenografts in vivo. Thus, dual degradation of WDR5 and Ikaros is a promising anti-cancer strategy.
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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 Socratic graph.