ArticleJournal of the American Chemical Society2025
Dual-Action-Only PROTACs.
Article in Journal of the American Chemical Society, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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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
14 citing papers in PubMed.
- Targeted proteoform degradation for precision drug design, delivery, and therapy.Drug delivery · 2026Review
- Advancing PROTAC therapeutics through chemistry-guided design of smart delivery systems.Acta pharmacologica Sinica · 2026Review
- An antibody-PROTAC conjugate targets BRD4/c-Myc/PD-L1 to enhance immunotherapy efficacy in triple-negative breast cancer.Cell reports. Medicine · 2026Article
- Protein-protein interaction-mediated signaling networks in ischemic stroke: from molecular mechanisms to therapeutic strategies.Acta pharmacologica Sinica · 2026Review
- Tricarbonyl Rhenium-Based PROTACs Degrade the SARS-CoV-2 Mpro Protease.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Article
- Dual PROTACs Versus Dual Inhibitors in Oncology: A Medicinal Chemistry and Linker Design Perspective.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Enzyme-Induced Supramolecular Proteolysis-Targeting Chimeras Enable Tumor-Targeted Protein Degradation.JACS Au · 2026Article
- Cathepsin L as a Driver of Tumour Invasion and a Novel Therapeutic Target in Ovarian Cancer.Cancers · 2026Review
- The application of drug delivery systems based on targeted protein degradation chimeras in disease treatment strategies.Journal of nanobiotechnology · 2026Review
- A Spatiotemporally Controlled Nanoplatform for Photothermal BRD4 Degradation Enables Synergistic Cancer Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- RuPHOTACs Provide Photocontrol Over Protein Degradation with Optimized Properties for Biological Applications.Research square · 2026Article
- Research progress and future perspectives in proteolysis-targeting chimeras.Frontiers in pharmacology · 2026Review
- Cul5: immune cell function and therapeutic potential.Frontiers in immunology · 2026Review
- Targeted protein degradation of HSP90 and associated proteins for cancer therapyRSC medicinal chemistry · 2025Review
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Proteolysis targeting chimera (PROTAC)-based degraders are highly potent pseudocatalytic drugs, but on-target off-site homing could yield undesirable consequences. We report here a generalizable AND-logic gated PROTAC, where the concurrent presence of two different disease-relevant endogenous stimuli liberates an active protein degrader. We design Dual-Action-Only PROTAC (DAO-PROTAC) molecules that are dormant and can only be activated in the presence of both hypoxia and cathepsin-L to degrade the protein of interest (POI). We also show that the dormancy of DAO-PROTACs translates to considerable mitigation of cytotoxicity, demonstrating the potential advantages over the corresponding free PROTAC and single-stimulus triggerable pro-PROTACs.
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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.