ArticleJournal of the American Chemical Society2023
Discovery of a Potent and Selective Targeted NSD2 Degrader for the Reduction of H3K36me2.
Article in Journal of the American Chemical Society, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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Who cites it
26 citing papers in PubMed, 58 citations in OpenAlex.
- NSD Histone Methyltransferases in Solid Tumors: Biological Functions, Oncogenic Mechanisms and Therapeutic Targeting.International journal of molecular sciences · 2026Review
- Proteomics-Driven Strategies for Proximity-Inducing Drug Discovery.Angewandte Chemie (International ed. in English) · 2026Review
- Aryl Aldehyde-Anchored Small Molecules Recruit FBXO22 for Targeted Degradation of NSD2.Journal of medicinal chemistry · 2026Article
- Structural basis of NSD2 degradation via targeted recruitment of SCF-FBXO22.Nature communications · 2026Article
- Genetic loss of CHD1 regulates distinct histone post-translational modifications in the development of castration-resistant prostate cancer.Neoplasia (New York, N.Y.) · 2026Article
- Article
- NSD Family-Mediated H3K36 Methylation in Human Cancer: Mechanisms and Therapeutic Opportunities.Biomedicines · 2025Review
- Nucleosome context regulates chromatin reader preference.Nucleic acids research · 2025Article
- Mode of action of a DCAF16-recruiting targeted glue that can selectively degrade BRD9.Nature communications · 2025Article
- Chromatin Regulatory Targets for Anticancer Therapeutics.Chemical reviews · 2025Review
- Structural and Molecular Insight into the PWWP1 Domain of NSD2 from the Discovery of Novel Binders Via DNA-Encoded Library Screening.ACS medicinal chemistry letters · 2025Article
- Research status of small molecule inhibitors, probes, and degraders of NSDs: a comprehensive review.Future medicinal chemistry · 2025Review
- Designing the Proteome with Chemical Tools: Degrons and Beyond.Chembiochem : a European journal of chemical biology · 2025Review
- NSD proteins in anti-tumor immunity and their therapeutic targeting by protein degraders.Cellular and molecular life sciences : CMLS · 2025Review
- Covalent Proximity Inducers.Chemical reviews · 2025Review
- Histone-modifying enzymes as drivers and therapeutic targets in androgen-resistant prostate cancer.Frontiers in endocrinology · 2025Review
- Novel dual-targeting inhibitors of NSD2 and HDAC2 for the treatment of liver cancer: structure-based virtual screening, molecular dynamics simulation, andJournal of enzyme inhibition and medicinal chemistry · 2024Article
- Recruitment of FBXO22 for targeted degradation of NSD2.Nature chemical biology · 2024Article
- Epithelial NSD2 maintains FMO-mediated taurine biosynthesis to prevent intestinal barrier disruption.Clinical and translational medicine · 2024Article
- Epigenetic therapies targeting histone lysine methylation: complex mechanisms and clinical challenges.The Journal of clinical investigation · 2024Review
Corrections and comments
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Authors and funding
19 authors at 4 institutions in 2 countries.
Funding
Abstract
Nuclear receptor-binding SET domain-containing 2 (NSD2) plays important roles in gene regulation, largely through its ability to dimethylate lysine 36 of histone 3 (H3K36me2). Despite aberrant activity of NSD2 reported in numerous cancers, efforts to selectively inhibit the catalytic activity of this protein with small molecules have been unsuccessful to date. Here, we report the development of UNC8153, a novel NSD2-targeted degrader that potently and selectively reduces the cellular levels of both NSD2 protein and the H3K36me2 chromatin mark. UNC8153 contains a simple warhead that confers proteasome-dependent degradation of NSD2 through a novel mechanism. Importantly, UNC8153-mediated reduction of H3K36me2 through the degradation of NSD2 results in the downregulation of pathological phenotypes in multiple myeloma cells including mild antiproliferative effects in MM1.S cells containing an activating point mutation and antiadhesive effects in KMS11 cells harboring the t(4;14) translocation that upregulates NSD2 expression.
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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.