ArticleCancer discovery2022
Small-Molecule Inhibition of the Acyl-Lysine Reader ENL as a Strategy against Acute Myeloid Leukemia.
Article in Cancer discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 38 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
38 citing papers in PubMed, 55 citations in OpenAlex.
- High-throughput ligand diversification to discover chemical inducers of proximity.Nature chemical biology · 2026Article
- Article
- Discovery of a Highly Potent and Selective ENL Degrader.Journal of medicinal chemistry · 2026Article
- Learning from Yeast-How YEATS Domain Proteins Read Epigenetic Marks Driving Oncogenic Programs in Gastrointestinal Tumors.Digestive diseases and sciences · 2026Article
- A chemical-genetic interaction between PAF1 and ENL/AF9 YEATS inhibition.RSC chemical biology · 2026Article
- Chromatin Regulatory Targets for Anticancer Therapeutics.Chemical reviews · 2025Review
- Functional Roles and Mechanistic Insights of YEATS Domain Proteins in Digestive System Tumors.Digestive diseases and sciences · 2025Review
- Review
- Development of Chemical Tools for the Human YEATS Domain.ACS chemical biology · 2025Review
- Editor's Note: Small-Molecule Inhibition of the Acyl-Lysine Reader ENL as a Strategy against Acute Myeloid Leukemia.Cancer discovery · 2025Article
- Perturbing LSD1 and WNT rewires transcription to synergistically induce AML differentiation.Nature · 2025Article
- YEATS2: a novel cancer epigenetic reader and potential therapeutic target.Cancer cell international · 2025Review
- Nuclear Control of Mitochondrial Homeostasis and Venetoclax Efficacy in AML via COX4I1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Prioritization of Eleven-Nineteen-Leukemia Inhibitors as Orally Available Drug Candidates for Acute Myeloid Leukemia.Journal of medicinal chemistry · 2024Article
- Epigenetics-targeted drugs: current paradigms and future challenges.Signal transduction and targeted therapy · 2024Review
- MLL oncoprotein levels influence leukemia lineage identities.Nature communications · 2024Article
- Epigenetic therapies targeting histone lysine methylation: complex mechanisms and clinical challenges.The Journal of clinical investigation · 2024Review
- Histone methyltransferase KMT2A: Developmental regulation to oncogenic transformation.The Journal of biological chemistry · 2024Review
- A potent and selective ENL degrader suppresses oncogenic gene expression and leukemia progression.Science advances · 2024Article
- Condensate-Promoting ENL Mutation Drives Tumorigenesis In Vivo Through Dynamic Regulation of Histone Modifications and Gene Expression.Cancer discovery · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
32 authors at 11 institutions in 3 countries.
Funding
Abstract
The chromatin reader eleven-nineteen leukemia (ENL) has been identified as a critical dependency in acute myeloid leukemia (AML), but its therapeutic potential remains unclear. We describe a potent and orally bioavailable small-molecule inhibitor of ENL, TDI-11055, which displaces ENL from chromatin by blocking its YEATS domain interaction with acylated histones. Cell lines and primary patient samples carrying MLL rearrangements or NPM1 mutations are responsive to TDI-11055. A CRISPR-Cas9-mediated mutagenesis screen uncovers an ENL mutation that confers resistance to TDI-11055, validating the compound's on-target activity. TDI-11055 treatment rapidly decreases chromatin occupancy of ENL-associated complexes and impairs transcription elongation, leading to suppression of key oncogenic gene expression programs and induction of differentiation. In vivo treatment with TDI-11055 blocks disease progression in cell line- and patient-derived xenograft models of MLL-rearranged and NPM1-mutated AML. Our results establish ENL displacement from chromatin as a promising epigenetic therapy for molecularly defined AML subsets and support the clinical translation of this approach. SIGNIFICANCE: AML is a poor-prognosis disease for which new therapeutic approaches are desperately needed. We developed an orally bioavailable inhibitor of ENL, demonstrated its potent efficacy in MLL-rearranged and NPM1-mutated AML, and determined its mechanisms of action. These biological and chemical insights will facilitate both basic research and clinical translation. This article is highlighted in the In This Issue feature, p. 2483.
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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.