ArticleScience advances2022
Hypoxia deactivates epigenetic feedbacks via enzyme-derived clicking proteolysis-targeting chimeras.
Article in Science advances, 2022. 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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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.
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Who cites it
26 citing papers in PubMed, 63 citations in OpenAlex.
- Advancing PROTAC therapeutics through chemistry-guided design of smart delivery systems.Acta pharmacologica Sinica · 2026Review
- Nitro Reduction-Based RNA Control and Ultrafast Release.Angewandte Chemie (International ed. in English) · 2026Article
- In Situ Bioorthogonal Synthesis of PROTACs via Dual-Responsive Cleavage for Synergistic Photo-Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Delivering Degradation: Nanomedicine and Programmable Proximity Platforms for Targeted Protein Degradation.Pharmaceutics · 2026Review
- Enzyme-Induced Supramolecular Proteolysis-Targeting Chimeras Enable Tumor-Targeted Protein Degradation.JACS Au · 2026Article
- Mechanisms and Design Principles of Proteolysis-Targeting Chimeras and Their Emerging Applications.ACS pharmacology & translational science · 2026Review
- RuPHOTACs Provide Photocontrol Over Protein Degradation with Optimized Properties for Biological Applications.Research square · 2026Article
- Proteolysis-targeting chimera (PROTAC) nanomedicines toward cancer treatment: From synthesis to therapeutic delivery.Biomaterials · 2026Review
- Evolution of proteolysis-targeting chimeras (PROTAC) technology to overcome challenges of antimicrobial resistance.npj antimicrobials and resistance · 2025Review
- Hypoxia-activated paclitaxel prodrugs enable PD-L1 degradation to potentiate cancer chemo-immunotherapy.Journal of nanobiotechnology · 2025Article
- Rational design of the linkers in targeting chimeras.Chemical science · 2025Review
- Recent Advances in the Development of Pro-PROTAC for Selective Protein Degradation.Pharmaceutics · 2025Review
- Photodynamic enhancement of PROTAC prodrug activation in hypoxic tumors.Acta pharmaceutica Sinica. B · 2025Article
- Article
- Endogenous tyrosinase-catalyzed therapeutics.Nature communications · 2025Article
- Light-Controlled Intracellular Synthesis of Poly(luciferin) Polymers Induces Cell Paraptosis.Journal of the American Chemical Society · 2025Article
- Conditional PROTAC: Recent Strategies for Modulating Targeted Protein Degradation.ChemMedChem · 2024Review
- Article
- New-generation advanced PROTACs as potential therapeutic agents in cancer therapy.Molecular cancer · 2024Review
- Click chemistry in the development of PROTACs.RSC chemical biology · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epigenetic mediation through bromodomain and extraterminal (BET) proteins have progressively translated protein imbalance into effective cancer treatment. Perturbation of druggable BET proteins through proteolysis-targeting chimeras (PROTACs) has recently contributed to the discovery of effective therapeutics. Unfortunately, precise and microenvironment-activatable BET protein degradation content with promising tumor selectivity and pharmacological suitability remains elusive. Here, we present an enzyme-derived clicking PROTACs (ENCTACs) capable of orthogonally cross-linking two disparate small-molecule warhead ligands that recognize BET bromodomain-containing protein 4 (BRD4) protein and E3 ligase within tumors only upon hypoxia-induced activation of nitroreductase enzyme. This localized formation of heterobifunctional degraders promotes specific down-regulation of BRD4, which subsequently alters expression of epigenetic targets and, therefore, allows precise modulation of hypoxic signaling in live cells, zebrafish, and living mice with solid tumors. Our activation-feedback system demonstrates compelling superiorities and may enable the PROTAC technology with more flexible practicality and druggable potency for precision medicine in the near future.
Identifiers
What OpenQuestion holds
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.