ReviewNature reviews. Drug discovery2023
Delivering on the promise of protein degraders.
Review in Nature reviews. Drug discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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
34 citing papers in PubMed.
- Post-translational modification-regulating biomaterials for regeneration.Bioactive materials · 2026Review
- Advancing PROTAC therapeutics through chemistry-guided design of smart delivery systems.Acta pharmacologica Sinica · 2026Review
- Molecular Glue Degraders Enhance CAPRIN1-Dependent Lysosomal Degradation of APP and Reduce Amyloid β in Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A Single-Amino-Acid Ligand for LAT1: A Minimalist and Modular Platform for Lysosome-Targeted Degradation of Membrane Proteins.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Breast Cancer: Epidemiology, Molecular Classification, Diagnostics and Evolving Treatment Paradigms.Molecules (Basel, Switzerland) · 2026Review
- The expanding role of formulations to enable oral delivery of poorly water-soluble drugs.Nature reviews. Drug discovery · 2026Review
- Molecular engineering of lysosome-based degraders unveils a rapidly expanding therapeutic strategy.Autophagy · 2026Review
- Targeted degradation of c-Myc through the midnolin-proteasome pathway.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- PSMA-Targeting Chimeras for Cell-Type-Specific Degradation of Surface Immune Checkpoint Protein PD-L1.JACS Au · 2026Article
- Rational design of potent small-molecule SMARCA2/A4 degraders acting via the recruitment of FBXO22.Nature communications · 2025Article
- PROTAC-Mediated Degradation of TAF1 Induces Apoptosis in AML Cells and Inhibits Tumor Growth In Vivo.Molecular cancer therapeutics · 2025Article
- Fas apoptotic inhibitor molecule 2 mitigates metabolic dysfunction-associated fatty liver disease through autophagic CRTC2 degradation.Experimental & molecular medicine · 2025Article
- Targeted protein degradation in oncology: novel therapeutic opportunity for solid tumours?Molecular oncology · 2025Review
- Multi-omics analysis reveals RNA polymerase II degradation as a novel mechanism of PF-3758309's anti-tumor activity.Cell death discovery · 2025Article
- Targeted protein degradation for cancer therapy.Nature reviews. Cancer · 2025Review
- Preparation and Characterization of Ternary Complexes to Improve the Solubility and Dissolution Performance of a Proteolysis-Targeting Chimera Drug.Pharmaceutics · 2025Article
- Harnessing the SPOP E3 Ubiquitin Ligase via a Bridged Proteolysis Targeting Chimera (PROTAC) Strategy for Targeted Protein Degradation.Journal of medicinal chemistry · 2025Article
- Property-based optimisation of PROTACs.RSC medicinal chemistry · 2025Article
- A Kinetic Scout Approach Accelerates Targeted Protein Degrader Development.Angewandte Chemie (International ed. in English) · 2025Article
- Impact of Linker Composition on VHL PROTAC Cell Permeability.Journal of medicinal chemistry · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Over the past 3 years, the first bivalent protein degraders intentionally designed for targeted protein degradation (TPD) have advanced to clinical trials, with an initial focus on established targets. Most of these clinical candidates are designed for oral administration, and many discovery efforts appear to be similarly focused. As we look towards the future, we propose that an oral-centric discovery paradigm will overly constrain the chemical designs that are considered and limit the potential to drug novel targets. In this Perspective, we summarize the current state of the bivalent degrader modality and propose three categories of degrader designs, based on their likely route of administration and requirement for drug delivery technologies. We then describe a vision for how parenteral drug delivery, implemented early in research and supported by pharmacokinetic-pharmacodynamic modelling, can enable exploration of a broader drug design space, expand the scope of accessible targets and deliver on the promise of protein degraders as a therapeutic modality.
Indexed as
Identifiers
36810917What 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.