ArticleACS chemical biology2024
Targeted Protein Degradation through Recruitment of the CUL4 Complex Adaptor Protein DDB1.
Article in ACS chemical biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 40 citations in OpenAlex.
- DNA-Encoded Library (DEL) Selection Identifies a Distinct DDB1 Ligand Binding Site.ACS medicinal chemistry letters · 2026Article
- Targeting the RNA-binding motif protein 15 suppresses prostate cancer progression and hormone therapy resistance by promoting androgen receptor degradation.Molecular biomedicine · 2026Article
- Discovery of SKP2-Recruiting PROTACs for Target Protein Degradation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Induced proximity-based therapeutic modalities.Nature reviews. Drug discovery · 2026Review
- Advances in molecular glue degraders for targeted protein degradation: Focus on NEK7, WEE1, CDK2, GSPT1 and VAV1.Asian journal of pharmaceutical sciences · 2026Review
- Context Matters: E3 Ligase-Ligand Pairing Strategies for Optimized PROTAC Performance.Protein & cell · 2025Article
- Cysteine-reactive covalent chloro-N-acetamide ligands induce ferroptosis mediated cell death.EMBO reports · 2025Article
- Targeted Histone Deacetylase Degradation via Chemical Induced Proximity by Direct Recruitment of the CUL4 Complex Adaptor Protein DDB1.ACS medicinal chemistry letters · 2025Article
- DCAF16-Based Covalent Degradative Handles for the Modular Design of Degraders.ACS central science · 2025Article
- Identification of Actionable Targeted Protein Degradation Effector Sites through Site-Specific Ligand Incorporation-Induced Proximity (SLIP).Journal of the American Chemical Society · 2025Article
- High cereblon expression in neuroendocrine cancer confers vulnerability to GSPT1 molecular glue degrader.Experimental hematology & oncology · 2025Article
- Covalent Destabilizing Degrader of AR and AR-V7 in Androgen-Independent Prostate Cancer Cells.Journal of the American Chemical Society · 2025Article
- Linker-free PROTACs efficiently induce the degradation of oncoproteins.Nature communications · 2025Article
- Optimizing TPD-based oncology drug development: the critical role of PDR distribution in POI-positive cancer cells.Acta pharmaceutica Sinica. B · 2025Article
- PROteolysis TArgeting Chimeras (PROTACs) and beyond: targeted degradation as a new path to fight microbial pathogens.FEMS microbiology reviews · 2025Review
- Covalent Proximity Inducers.Chemical reviews · 2025Review
- Principles of paralog-specific targeted protein degradation engaging the C-degron E3 KLHDC2.Nature communications · 2024Article
- Pooled endogenous protein tagging and recruitment for systematic profiling of protein function.Cell genomics · 2024Article
- Ligand discovery by activity-based protein profiling.Cell chemical biology · 2024Review
- Dual role of targeting NAE1 in nasopharyngeal carcinoma: Antitumor effects yet inducing radiotherapy resistance.Heliyon · 2024Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Targeted protein degradation has arisen as a powerful therapeutic modality for eliminating proteins. Thus far, most heterobifunctional proteolysis targeting chimeras (PROTACs) have utilized recruiters against substrate receptors of Cullin RING E3 ubiquitin ligases, such as cereblon and VHL. However, previous studies have surprisingly uncovered molecular glue degraders that exploit a CUL4 adaptor protein DDB1 to degrade neosubstrate proteins. Here, we sought to investigate whether DDB1 recruiters can be discovered that can be exploited for PROTAC applications. We utilized activity-based protein profiling and cysteine chemoproteomic screening to identify a covalent recruiter that targets C173 on DDB1 and exploited this recruiter to develop PROTACs against BRD4 and androgen receptor (AR). We demonstrated that the BRD4 PROTAC results in selective degradation of the short BRD4 isoform over the long isoform in a proteasome, NEDDylation, and DDB1-dependent manner. We also demonstrated degradation of AR with the AR PROTAC in prostate cancer cells. Our study demonstrated that covalent chemoproteomic approaches can be used to discover recruiters against Cullin RING adapter proteins and that these recruiters can be used for PROTAC applications to degrade neo-substrates.
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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.