ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2023
Targeted Degradation of PRC1 Components, BMI1 and RING1B, via a Novel Protein Complex Degrader Strategy.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- Targeted degradation of Influenza a virus nucleoprotein via aptamer-based PROTACs for antiviral therapy.Virulence · 2026Article
- An EZH2-SREBP2 axis promotes cholesterol biosynthesis and represents a noncanonical vulnerability in tumorigenesis.Nature cell biology · 2026Article
- Hydrophobic Tag Degraders Overcome Endocrine-Resistant Breast Cancer by Recruiting HSP27-Mediated E3 Ligase Complex for ERα Proteasomal Degradation.Angewandte Chemie (International ed. in English) · 2026Article
- PROTACs for Collateral Degradation: Is It Time to Back Up the Bus?ACS medicinal chemistry letters · 2026Review
- Mono-ubiquitination of histone H2A lysine 119 (H2AK119Ub): its multifaceted role in biology and implication in diseases.MedScience · 2026Review
- Chromatin Regulatory Targets for Anticancer Therapeutics.Chemical reviews · 2025Review
- Harnessing the SPOP E3 Ubiquitin Ligase via a Bridged Proteolysis Targeting Chimera (PROTAC) Strategy for Targeted Protein Degradation.Journal of medicinal chemistry · 2025Article
- Development of PRC1 Inhibitors Employing Fragment-Based Approach and NMR-Guided Optimization.Journal of medicinal chemistry · 2025Article
- An epigenetic pathway regulates MHC-II expression and function in B cell lymphoma models.The Journal of clinical investigation · 2025Article
- Sustained inactivation of the Polycomb PRC1 complex induces DNA repair defects and genomic instability in epigenetic tumors.Histochemistry and cell biology · 2024Article
- Discovery and Characterization of a Novel Cereblon-Recruiting PRC1 Bridged PROTAC Degrader.Journal of medicinal chemistry · 2024Article
- Sustained inactivation of the Polycomb PRC1 complex induces DNA repair defects and genomic instability in epigenetic tumors.Research square · 2024Article
- Discovery of a novel, highly potent EZH2 PROTAC degrader for targeting non-canonical oncogenic functions of EZH2.European journal of medicinal chemistry · 2024Article
- Degraders in epigenetic therapy: PROTACs and beyond.Theranostics · 2024Review
- Targeting reversible post-translational modifications with PROTACs: a focus on enzymes modifying protein lysine and arginine residues.Journal of enzyme inhibition and medicinal chemistry · 2023Review
- Acetylation Targeting Chimera Enables Acetylation of the Tumor Suppressor p53.Journal of the American Chemical Society · 2023Article
- Chemically induced degradation of epigenetic targets.Chemical Society reviews · 2023Review
- Targeted Degradation of PRC1 Components, BMI1 and RING1B, via a Novel Protein Complex Degrader Strategy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Polycomb repressive complex 1 (PRC1) is an essential epigenetic regulator that mainly controls histone H2A Lys119 mono-ubiquitination (H2AK119ub). B cell-specific Moloney murine leukemia virus Integration site 1 (BMI1) and really interesting new gene 1B (RING1B) are PRC1 core components and play critical roles in the development of various cancers. However, therapeutic agents targeting PRC1 are very limited. In this study, MS147, the first degrader of PRC1 core components, BMI1 and RING1B, is discovered via a novel protein complex degradation strategy that utilizes the target protein's interacting partner protein (embryonic ectoderm development (EED)). MS147, which comprises an EED small-molecule binder linked to a ligand of the E3 ligase von Hippel-Lindau (VHL), degrades BMI1/RING1B in an EED-, VHL-, ubiquitination-, and time-dependent manner. MS147 preferentially degrades BMI1/RING1B over polycomb repressive complex 2 (PRC2) core components. Consequently, MS147 effectively reduces H2AK119ub, but not histone H3 Lys27 tri-methylation (H3K27me3), which is catalyzed by PRC2. Furthermore, MS147 effectively inhibits the proliferation of cancer cell lines that are insensitive to PRC2 inhibitors/degraders. Overall, this study provides a novel BMI1/RING1B degrader, which is a useful chemical tool to further investigate the roles of PRC1 in cancer, and a novel protein complex degradation strategy, which can potentially expand the degradable human proteome.
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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.