ReviewNature reviews. Chemistry2026
Lessons learned in linking PROTACs from discovery to the clinic.
Review in Nature reviews. Chemistry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed.
- DNA polymerase theta (Polθ): a novel candidate for targeted cancer therapy.Cancer biology & therapy · 2026Review
- Context matters in PROTAC design: navigating the trade-off between degradation and developability.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Article
- Vepdegestrant: the first FDA-approved oral PROTAC and a milestone in targeted protein degradation.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Article
- Performance of Rilpivirine-Based Hydrophobic Tags and PROTACs Directed Against HIV-1 Reverse Transcriptase.bioRxiv : the preprint server for biology · 2026Article
- Aptamer-Based Heterobifunctional Targeted Degraders in Disease Treatment.Molecules (Basel, Switzerland) · 2026Review
- Autophagy modulation in cancer.Nature reviews. Drug discovery · 2026Review
- Identification and Studies of Highly Potent and Selective Heterobifunctional Galectin‑3 Degraders.ACS medicinal chemistry letters · 2026Article
- FDA Approval of the First-Ever PROTAC: Vepdegestrant (ARV-471) Marks a New Era in Targeted Protein Degradation.Journal of medicinal chemistry · 2026Article
- Design, synthesis, and biological characterization of a hydrophobic tagging EGFR degrader for the treatment of non-small-cell lung cancer.Molecular diversity · 2026Article
- Eyes Toward the Clinic: Selective Inhibition and Degradation Approaches to Bromodomain-Containing Proteins.Chembiochem : a European journal of chemical biology · 2026Review
- Targeted protein degradation: bridging chemical biology and clinical translation.Acta pharmacologica Sinica · 2026Review
- ALK rearrangements and resistance mutations in non-small cell lung cancer: molecular mechanisms and therapeutic implications.Cancer chemotherapy and pharmacology · 2026Review
- Discovery of Dihydropyrimido-Pyrimidine-Based Bone Marrow Tyrosine Kinase Gene in Chromosome X Protein Proteolysis-Targeting Chimeras for the Treatment of Prostate Cancer.ACS medicinal chemistry letters · 2026Article
- Research progress and future perspectives in proteolysis-targeting chimeras.Frontiers in pharmacology · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Targeted protein degradation has the potential to deliver greater efficacy than conventional receptor antagonists or enzyme inhibitors and address previously undruggable targets. This has driven a recent surge of interest in protein degradation modalities. Bifunctional degraders, specifically proteolysis targeting chimeras (PROTACs), have become a key modality in the protein degrader space, despite the physicochemical challenges they present in achieving oral bioavailability. In this Review, we discuss the lessons learned to date in the optimization of PROTACs, with particular emphasis on the role of the linker region, including its role in optimization of pharmacology, impact on oral bioavailability, and influence on metabolic fate. The evolution from pharmacological tools to an established clinical modality, and the lessons that can be drawn from the preclinical data and the first cohort of PROTACs to reach the clinic, is discussed.
Indexed as
Identifiers
41388140What Socratic 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 Socratic graph.