ArticleNature communications2020
Enhancing intracellular accumulation and target engagement of PROTACs with reversible covalent chemistry.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 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
93 citing papers in PubMed, 198 citations in OpenAlex.
- Context matters in PROTAC design: navigating the trade-off between degradation and developability.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Unraveling the secrets of novel PROTACs to improve degradation efficacy.Molecular diversity · 2026Review
- Advancing PROTAC therapeutics through chemistry-guided design of smart delivery systems.Acta pharmacologica Sinica · 2026Review
- Nanotechnology-Enabled Targeted Protein Degradation: Strategies, Opportunities, and Challenges.Small methods · 2026Review
- Proteolysis Targeting Chimeric-Based Technology in Myeloma and Lymphoma.Molecular cancer therapeutics · 2026Review
- Unlocking the ferroptotic window: Lipidomic rewiring and metabolic addiction in EMT-driven breast cancer resistance.Cell death discovery · 2026Review
- Reductive death is averted by a conserved de novo lipogenic switch.Molecular cell · 2026Article
- Ultrahigh-Throughput Liquid Chromatography with Tandem Mass Spectrometry Method for Targeted Protein Degradation Compound Screening Using the Orbitrap Astral Mass Spectrometer.Journal of proteome research · 2026Article
- Methods to Study the Molecular Mechanism and Drive the Design of Protein Degraders.Chemical reviews · 2026Review
- An HDAC4-specific PROTAC degrader achieves radiation sensitization by enhancing ferroptosis in lung cancer.Nature communications · 2026Article
- Advances in BRET probes for intracellular target engagement studies.Nature chemical biology · 2026Review
- Protein structural dynamics in covalent drug design: insights from irreversible and reversible covalent inhibitors.RSC chemical biology · 2026Review
- Antiviral drug discovery and development: challenges and future directions.Signal transduction and targeted therapy · 2026Review
- Sub-stoichiometric Degradation is Dispensable for Potent PROTACs: A Case Study for Irreversible Covalent BTK Degraders.bioRxiv : the preprint server for biology · 2026Article
- Review
- A Gold-PROTAC Degrades the Oncogenic Tyrosine Kinase MERTK: Insights into the Degradome from a Steady-State System.ACS chemical biology · 2026Article
- Integrated computational screen and validation of thalidomide-based PROTACs targeting SARS-CoV-2 main protease.RSC medicinal chemistry · 2026Article
- Exploiting Pharmacokinetic/Pharmacodynamic Methods for Optimizing and Accelerating Drug Development of Innovative Anti-Infectives.ChemMedChem · 2026Review
- Targeting ubiquitination in disease and therapy.Signal transduction and targeted therapy · 2025Review
- The Current Toolbox for Covalent Inhibitors: From Hit Identification to Drug Discovery.JACS Au · 2025Review
33 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 6 institutions in 1 country.
Funding
Abstract
Current efforts in the proteolysis targeting chimera (PROTAC) field mostly focus on choosing an appropriate E3 ligase for the target protein, improving the binding affinities towards the target protein and the E3 ligase, and optimizing the PROTAC linker. However, due to the large molecular weights of PROTACs, their cellular uptake remains an issue. Through comparing how different warhead chemistry, reversible noncovalent (RNC), reversible covalent (RC), and irreversible covalent (IRC) binders, affects the degradation of Bruton's Tyrosine Kinase (BTK), we serendipitously discover that cyano-acrylamide-based reversible covalent chemistry can significantly enhance the intracellular accumulation and target engagement of PROTACs and develop RC-1 as a reversible covalent BTK PROTAC with a high target occupancy as its corresponding kinase inhibitor and effectiveness as a dual functional inhibitor and degrader, a different mechanism-of-action for PROTACs. Importantly, this reversible covalent strategy is generalizable to improve other PROTACs, opening a path to enhance PROTAC efficacy.
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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.