ReviewExploration of targeted anti-tumor therapy2020
Current strategies for the design of PROTAC linkers: a critical review.
Review in Exploration of targeted anti-tumor therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 173 papers.
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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
173 citing papers in PubMed.
- Targeted proteoform degradation for precision drug design, delivery, and therapy.Drug delivery · 2026Review
- Evolving CRBN ligands enhance the drug-like properties of protein degraders.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Limiting Trial-and-Error: Linker-Based 2D Descriptor Analysis to Support Very Early Proteolysis-Targeting Chimeras Design.ChemMedChem · 2026Article
- A protein-foldamer supramolecular synthon for self-assembled hybrid architectures.Nature chemistry · 2026Article
- Advancing PROTAC therapeutics through chemistry-guided design of smart delivery systems.Acta pharmacologica Sinica · 2026Review
- Linker Optimization of cMYC RIBOTAC for Efficient cMYC Modulation.ChemMedChem · 2026Article
- Hydrophobic Tag Protein Degraders: An Emerging Therapeutic Strategy for Cancer.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Supramolecular Degraders: An Emerging Paradigm in Targeted Protein Degradation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- A General Photoredox Platform for the Hydroarylation of Olefins.Journal of the American Chemical Society · 2026Article
- Discovery and Development of First-in-Class Cereblon-Recruiting RIPK1 Degraders.Journal of medicinal chemistry · 2026Article
- Pocket-PROTACs: an interpretable pocket-aware deep learning framework for predicting PROTAC-induced protein degradation.Bioinformatics (Oxford, England) · 2026Article
- Dual PROTACs Versus Dual Inhibitors in Oncology: A Medicinal Chemistry and Linker Design Perspective.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Eyes Toward the Clinic: Selective Inhibition and Degradation Approaches to Bromodomain-Containing Proteins.Chembiochem : a European journal of chemical biology · 2026Review
- Assays for Measuring the Cell Permeability of Proteolysis-Targeting Chimeras (PROTACs): Performance, Correlations, Applicability and Recommendations.Molecular pharmaceutics · 2026Article
- Targeted Protein Degradation of NUDT5 Dissociates Catalytic Inhibition from Protein Loss in 6-Thioguanine Response.Nature communications · 2026Article
- Understanding and Overcoming Antibody-Drug Conjugate Resistance: Biological Mechanisms and Emerging Analytical Frameworks in Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Metastable Protein-Protein Interactions as a Design Principle for PROTACs: Insights from the RIPK1-VHL System.JACS Au · 2026Article
- An HDAC4-specific PROTAC degrader achieves radiation sensitization by enhancing ferroptosis in lung cancer.Nature communications · 2026Article
- Proteolysis-targeting chimera (PROTAC) in cancer: design principles and applications on "undruggable" targets.Biomarker research · 2026Review
- Branching beyond bifunctional linkers: synthesis of macrocyclic and trivalent PROTACs.Nature protocols · 2026Review
113 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PROteolysis TArgeting Chimeras (PROTACs) are heterobifunctional molecules consisting of two ligands; an "anchor" to bind to an E3 ubiquitin ligase and a "warhead" to bind to a protein of interest, connected by a chemical linker. Targeted protein degradation by PROTACs has emerged as a new modality for the knock down of a range of proteins, with the first agents now reaching clinical evaluation. It has become increasingly clear that the length and composition of the linker play critical roles on the physicochemical properties and bioactivity of PROTACs. While linker design has historically received limited attention, the PROTAC field is evolving rapidly and currently undergoing an important shift from synthetically tractable alkyl and polyethylene glycol to more sophisticated functional linkers. This promises to unlock a wealth of novel PROTAC agents with enhanced bioactivity for therapeutic intervention. Here, the authors provide a timely overview of the diverse linker classes in the published literature, along with their underlying design principles and overall influence on the properties and bioactivity of the associated PROTACs. Finally, the authors provide a critical analysis of current strategies for PROTAC assembly. The authors highlight important limitations associated with the traditional "trial and error" approach around linker design and selection, and suggest potential future avenues to further inform rational linker design and accelerate the identification of optimised PROTACs. In particular, the authors believe that advances in computational and structural methods will play an essential role to gain a better understanding of the structure and dynamics of PROTAC ternary complexes, and will be essential to address the current gaps in knowledge associated with PROTAC design.
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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.