ReviewBritish journal of pharmacology2020
Proteolysis-targeting chimeras in drug development: A safety perspective.
Review in British journal of pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
91 citing papers in PubMed, 1 synthesis or guideline pooled it, 207 citations in OpenAlex.
- Emerging protein degradation strategies: expanding the scope to extracellular and membrane proteins.Theranostics · 2021Pooled it
- Proteome-guided drug discovery maps and mitigates therapeutic degrader toxicity.Nature chemical biology · 2026Article
- Aptamer-Based Heterobifunctional Targeted Degraders in Disease Treatment.Molecules (Basel, Switzerland) · 2026Review
- BTK Inhibitors for the Treatment of Mantle Cell Lymphoma-Current Status and Perspectives.Cancers · 2026Review
- An antibody-PROTAC conjugate targets BRD4/c-Myc/PD-L1 to enhance immunotherapy efficacy in triple-negative breast cancer.Cell reports. Medicine · 2026Article
- Proteolysis Targeting Chimeric-Based Technology in Myeloma and Lymphoma.Molecular cancer therapeutics · 2026Review
- Safety considerations for cereblon-recruiting targeted protein degraders.Nature reviews. Drug discovery · 2026Review
- Chemical Epigenetics: Small Molecules Targeting Chromatin Modifiers in Disease Modulation.Cell biochemistry and biophysics · 2026Review
- Enzyme-Induced Supramolecular Proteolysis-Targeting Chimeras Enable Tumor-Targeted Protein Degradation.JACS Au · 2026Article
- Reimagining GSK-3β Therapeutics in Alzheimer's Disease: From Inhibition to Activity Normalization and Targeted Degradation.Journal of molecular neuroscience : MN · 2026Review
- Fulfilling multiple roles in PROTAC design: The emerging potential of oligonucleotides.European journal of medicinal chemistry · 2026Review
- A dihydrouracil CRBN ligand mitigates IMiD associated safety liabilities in heterobifunctional targeted protein degrader.Nature communications · 2026Article
- SonoPIN enables precise, noninvasive, and efficient intracellular delivery of PROTACs.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Spatiotemporally controlled ferritin-targeting PROTAC nanoplatform for visualized manipulation of endogenous "Iron pool" in pancreatic cancer therapy.Materials today. Bio · 2026Article
- pH-Activatable engineered nanoparticle-based selective hexokinase 2 degrader provokes GSDME-dependent pyroptosis for cancer therapy.Acta pharmaceutica Sinica. B · 2026Article
- Targeted protein degradation of HSP90 and associated proteins for cancer therapyRSC medicinal chemistry · 2025Review
- Recent advances in targeting protein degradation for tumor immunotherapy.Journal of hematology & oncology · 2025Review
- Next-Generation Proteolysis-Targeting Chimeras in Precision Oncology: Multifunctional Designs, Emerging Modalities, and Translational Prospects in Targeted Protein Degradation.Drug development research · 2025Review
- Discovery of a Proteolysis Targeting Chimera for TRKA and RET-derived oncoproteins.Scientific reports · 2025Article
- Review
31 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
9 authors at 4 institutions in 8 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proteolysis-targeting chimeras are a new drug modality that exploits the endogenous ubiquitin proteasome system to degrade a protein of interest for therapeutic benefit. As the first-generation of proteolysis-targeting chimeras have now entered clinical trials for oncology indications, it is timely to consider the theoretical safety risks inherent with this modality which include off-target degradation, intracellular accumulation of natural substrates for the E3 ligases used in the ubiquitin proteasome system, proteasome saturation by ubiquitinated proteins, and liabilities associated with the "hook effect" of proteolysis-targeting chimeras This review describes in vitro and non-clinical in vivo data that provide mechanistic insight of these safety risks and approaches being used to mitigate these risks in the next generation of proteolysis-targeting chimera molecules to extend therapeutic applications beyond life-threatening diseases.
Indexed as
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.