ArticleNature chemical biology2025
Polyvalent folate receptor-targeting chimeras for degradation of membrane proteins.
Article in Nature chemical biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 23 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.
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Who cites it
23 citing papers in PubMed.
- Lysosome-directed targeted protein degradation technologies for overcoming cancer drug resistance: mechanisms, design principles, and therapeutic opportunities.Drug delivery · 2026Review
- Unlocking the "undruggable": current landscape and emerging frontiers in lysosomal receptor-mediated protein degradation.Drug delivery · 2026Review
- ROS-Activatable "off-on" Fluorescent Prodrug Loaded Micelles for Targeted Therapy and in Situ Imaging of Breast Cancer Cells.International journal of pharmaceutics: X · 2026Article
- Targeted extracellular degradation of LRP8 promotes ferroptosis in cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- TROP2-Targeting Chimeras (TRTACs) for Tumor Cell-Selective Membrane Protein Degradation and Enhanced Drug Delivery.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeted Lysosomal Degradation of Extracellular and Membrane Proteins: From Receptor Hijacking to Programmable Endolysosomal Routing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Engineering Antibodies into Targeted Chimeras: From Recognition Modules to Programmable Degraders.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Assembly delivery of bioactive matters: Advances, challenges, and prospects.Journal of advanced research · 2026Review
- Nanotechnology-Enabled Targeted Protein Degradation: Strategies, Opportunities, and Challenges.Small methods · 2026Review
- 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
- A destination-driven framework for nanoparticle-enabled targeted protein degradation.Acta pharmaceutica Sinica. B · 2026Review
- Targeted protein degradation: bridging chemical biology and clinical translation.Acta pharmacologica Sinica · 2026Review
- Nano-enabled spatially selective protein degradation modulates lactate metabolism to potentiate antitumor immunity in liver cancer.Nature nanotechnology · 2026Article
- Lysosome-centered nanomedicine for cancer therapy: mechanisms, materials, and modalities.Journal of nanobiotechnology · 2026Review
- The application of drug delivery systems based on targeted protein degradation chimeras in disease treatment strategies.Journal of nanobiotechnology · 2026Review
- Prospects and advances of PROTAC in the treatment of hematologic malignancies.Experimental hematology & oncology · 2026Review
- Dynamic reprogramming of the tumor immune network via multicycle checkpoint degradation for cancer immunotherapy.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- DNA Nanoflower LYTACs Enable Efficient VEGF Degradation and Verteporfin Loading for Combined Therapy of Wet Age-Related Macular Degeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Aptamer-Mediated Covalent Dual Lysosome-Targeting Chimeras Enhance Targeted Degradation of Cell Surface Proteins.JACS Au · 2026Article
- Polymeric Lysosome-Targeting Chimeras (PolyTACs): Extracellular Targeted Protein Degradation without Co-Opting Lysosome-Targeting Receptors.Journal of the American Chemical Society · 2026Article
Corrections and comments
- Erratum issued
Authors and funding
13 authors.
Funding
Abstract
Lysosome-targeting chimeras (LYTACs) represent a revolutionary targeted protein degradation technology. However, the advancement of LYTACs faces substantial challenges due to the limited diversity of lysosome-trafficking receptors. In this study, we identified folate receptor α (FRα) as a new class of lysosome-trafficking receptors capable of facilitating the degradation of membrane proteins. Leveraging a polyvalent crosslinking strategy, we developed FRα-targeting chimeras (FRTACs), including epidermal growth factor receptor-targeting FR-Ctx and PD-L1-targeting FR-Atz. The optimized FRTACs demonstrated subnanomolar potency in eliminating cell-surface targets, with efficacy dependent on both FRα expression and lysosomal activity. Specifically, FR-Ctx inhibited cancer cell proliferation, while FR-Atz enhanced T cell-mediated cytotoxicity against tumor cells. FR-Atz exhibited robust PD-L1 degradation efficiency in vivo and elicited tumor-specific immune responses by reprogramming the tumor microenvironment from an immunosuppressive to an immunostimulatory state in both RM-1 and humanized B16F10 mouse models. These findings establish FRTACs as a promising platform for the design of tumor-targeting LYTACs.
Indexed as
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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.