ReviewSLAS discovery : advancing life sciences R & D2021
E3 Ligase Ligands for PROTACs: How They Were Found and How to Discover New Ones.
Review in SLAS discovery : advancing life sciences R & D, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 161 papers.
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Who cites it
161 citing papers in PubMed, 341 citations in OpenAlex.
- Evolving CRBN ligands enhance the drug-like properties of protein degraders.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- PROTACs in cancer therapy: targeted degradation of GPX4, PARP and epigenetic regulators.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Context matters in PROTAC design: navigating the trade-off between degradation and developability.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- The molecular glue CLEO4-88 inhibits the ACAA1 thiolase by induced binding to GID4.Nature chemical biology · 2026Article
- Advancing PROTAC therapeutics through chemistry-guided design of smart delivery systems.Acta pharmacologica Sinica · 2026Review
- Bridging E3 Ligase Binding and Targeted Degradation Through Fluorescence Polarization.International journal of molecular sciences · 2026Article
- Engineering Antibodies into Targeted Chimeras: From Recognition Modules to Programmable Degraders.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Cyclins and Cyclin-Dependent Kinases: Structure, Biological Functions, and Innovative Targeting Strategies in Cancer.MedComm · 2026Review
- E3 Ubiquitin Ligase Rsp5 Controls Lifestyle Transition and Pathogenicity inJournal of fungi (Basel, Switzerland) · 2026Article
- Pocket-PROTACs: an interpretable pocket-aware deep learning framework for predicting PROTAC-induced protein degradation.Bioinformatics (Oxford, England) · 2026Article
- Precision-Engineered PROTACs: Integrating Physical and Chemical Strategies for Targeted Cancer Therapy.Small (Weinheim an der Bergstrasse, Germany) · 2026Review
- Two Mechanisms One Molecule: Developing a 'Truly' Bifunctional Degrader Targeting Rpn13 and CRBN.Journal of the American Chemical Society · 2026Article
- COMPASS: A Computational Pipeline to Identify Linkers Predicting Ubiquitinable PROTAC-Induced Ternary Complexes.ChemMedChem · 2026Article
- Eyes Toward the Clinic: Selective Inhibition and Degradation Approaches to Bromodomain-Containing Proteins.Chembiochem : a European journal of chemical biology · 2026Review
- Identification of Clofibric Acid as a Synoviolin (SYVN1) Ligand for Proteolysis-Targeting Chimera (PROTAC) Development.ACS medicinal chemistry letters · 2026Article
- PROTAC-mediated regulation of programmed cell death: From molecular mechanisms to therapeutic breakthroughs.Innovation (Cambridge (Mass.)) · 2026Review
- HDAC3 in Alzheimer's Disease: established evidence, unresolved questions, and translational priorities.Molecular biology reports · 2026Review
- First Generation Proteolysis Targeting Chimeras (PROTACs) for the Treatment of Progeria.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Tipping the balance: NRF2's dual role in ferroptotic fate.Oncogenesis · 2026Review
- Self-Dimerization Induced Proximity Targeting Chimeras (SDIPTAC) Lead to DCAF1 Loss of Function and Inhibition of HIV Replication.Journal of medicinal chemistry · 2026Article
101 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bifunctional degrader molecules, also called proteolysis-targeting chimeras (PROTACs), are a new modality of chemical tools and potential therapeutics to understand and treat human disease. A required PROTAC component is a ligand binding to an E3 ubiquitin ligase, which is then joined to another ligand binding to a protein to be degraded via the ubiquitin-proteasome system. The advent of nonpeptidic small-molecule E3 ligase ligands, notably for von Hippel-Lindau (VHL) and cereblon (CRBN), revolutionized the field and ushered in the design of drug-like PROTACs with potent and selective degradation activity. A first wave of PROTAC drugs are now undergoing clinical development in cancer, and the field is seeking to extend the repertoire of chemistries that allow hijacking new E3 ligases to improve the scope of targeted protein degradation.Here, we briefly review how traditional E3 ligase ligands were discovered, and then outline approaches and ligands that have been recently used to discover new E3 ligases for PROTACs. We will then take an outlook at current and future strategies undertaken that invoke either target-based screening or phenotypic-based approaches, including the use of DNA-encoded libraries (DELs), display technologies and cyclic peptides, smaller molecular glue degraders, and covalent warhead ligands. These approaches are ripe for expanding the chemical space of PROTACs and usher in the advent of other emerging bifunctional modalities of proximity-based pharmacology.
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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.