ArticleAngewandte Chemie (International ed. in English)2025
The First-In-Class Deubiquitinase-Targeting Chimera Stabilizes and Activates cGAS.
Article in Angewandte Chemie (International ed. in English), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- dubTAGs enable on-demand stabilization for tunable and reversible control of endogenous protein levels.bioRxiv : the preprint server for biology · 2026Article
- Discovery of New OTUB1 Covalent Ligands via Structure-Activity Relationship Studies for Targeted Protein Stabilization.Journal of medicinal chemistry · 2026Article
- Targeted recruitment of USP15 enhances CTLA4 surface levels and restricts its degradation.Life science alliance · 2026Article
- Emerging biologic modalities for targeted protein degradation.The Journal of biological chemistry · 2026Review
- From Serendipity to Strategy: Rationalizing Molecular Glue Discovery and Proximity-Induced Pharmacology through Chemical Biology.Journal of the American Chemical Society · 2026Review
- From concept to application: Exploring the evolution and potential of DUBTAC technology.Acta pharmaceutica Sinica. B · 2026Review
- OTU deubiquitinases in disease: roles and targeting.Trends in molecular medicine · 2026Review
- [Potential of early diagnosis and targeted therapy for Klotho protein in chronic kidney disease].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Review
- Deubiquitinase-Targeting Chimeras Mediated Stabilization of Tumor Suppressive E3 Ligase Proteins as a Strategy for Cancer Therapy.Journal of the American Chemical Society · 2025Article
- Harnessing the Deubiquitinase USP1 for Targeted Protein Stabilization.Journal of the American Chemical Society · 2025Article
- USP28-Based Deubiquitinase-Targeting Chimeras for Cancer Treatment.Journal of the American Chemical Society · 2025Article
- Deubiquitinase-Targeting Chimeras (DUBTACs) as a Potential Paradigm-Shifting Drug Discovery Approach.Journal of medicinal chemistry · 2025Review
- The role of cGAS-STING pathway ubiquitination in innate immunity and multiple diseases.Frontiers in immunology · 2025Review
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Authors and funding
17 authors.
Funding
Abstract
Deubiquitinase-targeting chimera (DUBTAC) is a promising technology for inducing targeted protein stabilization (TPS). Despite its therapeutic potential, very few proteins have been stabilized by DUBTACs to date. The limited applicability of this technology is likely due to the modest DUBTAC-induced protein stabilization effect, and the scarcity of effective deubiquitinase ligands that can be harnessed for DUBTAC development. Here, we report the discovery of MS7829 and MS8588, the first-in-class DUBTACs of cGAS, a key component of the cGAS-STING pathway. While these DUBTACs are based on a cGAS inhibitor, they effectively stabilized cGAS and activated the cGAS/STING/IRF3 signaling. To develop these cGAS DUBTACs, we optimized EN523, an OTUB1 covalent ligand, into an improved ligand, MS5105. We validated MS5105 by generating a MS5105-based CFTR DUBTAC, which was approximately 10-fold more effective in stabilizing the ΔF508-CFTR mutant protein than the previously reported EN523-based CFTR DUBTAC. Overall, this work advances the DUBTAC technology for TPS.
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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.