ArticleNature communications2025
Linker-free PROTACs efficiently induce the degradation of oncoproteins.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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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.
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Who cites it
14 citing papers in PubMed.
- Context matters in PROTAC design: navigating the trade-off between degradation and developability.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Histone Deacetylase Meets Protein Degradation: Accelerating Anticancer Drug Discovery.Medicinal research reviews · 2026Review
- Engineering Polymeric Nano-PROTAC for Targeted Protein Degradation and Cancer Therapy.Polymer science & technology (Washington, D.C.) · 2026Review
- ALK rearrangements and resistance mutations in non-small cell lung cancer: molecular mechanisms and therapeutic implications.Cancer chemotherapy and pharmacology · 2026Review
- Review
- Molecular Dynamics-Guided Design and Chemoproteomic Profiling of Covalent Kinase Activity Probes.Journal of the American Chemical Society · 2026Article
- FBXO39 promotes LDHA-mediated aerobic glycolysis and colorectal cancer progression by p53 degradation.Journal of translational medicine · 2026Article
- Deubiquitinases in liver diseases: from mechanisms to targeted therapy.Science China. Life sciences · 2026Review
- PROTAC-based protein degradation: a window of opportunity for melanoma therapy.Journal of biomedical science · 2026Review
- Lessons learned in linking PROTACs from discovery to the clinic.Nature reviews. Chemistry · 2026Review
- The deubiquitinase USP35: from an oncogenic hub to a therapeutic target in human cancers.Frontiers in oncology · 2026Review
- The resilient subset: cancer stem cells at the core of immunotherapy resistance.Immunotherapy advances · 2026Review
- Tumor antigen PRAME promotes melanoma growth by inactivating p53 through the SIRT1-DBC1 axis.Oncogene · 2025Article
- The Role of Reactive Oxygen Species in Lung Cancer Development: Nanomedicine as a Therapeutic Strategy.Biomolecules · 2025Review
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
Proteolysis-targeting chimeras (PROTACs) present a potentially effective strategy against various diseases via selective proteolysis. How to increase the efficacy of PROTACs remains challenging. Here, we explore the necessity of the linker, which has been deemed as an integral part of heterobifunctional PROTACs. Adopting single amino acid-based degradation signals, we find that the linker is not a required feature of the PROTACs. Notably, the linker-free PROTAC, Pro-BA, exhibits superior efficacy over its linker-bearing counterparts in degrading EML4-ALK and inhibiting lung cancer cell growth, as Pro-BA induces a stronger interaction between the target and the E3 ubiquitin ligase. Pro-BA is a water-soluble, orally administered degrader that significantly inhibits the tumor growth in a xenograft mouse model. The broad applicability of this linker-free PROTAC strategy is further validated through the development of BCR-ABL degrader. Our study introduces a design paradigm for PROTACs, potentially facilitating the advancement of more efficient therapeutic degraders.
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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.