ArticleNature chemical biology2021
LYTACs that engage the asialoglycoprotein receptor for targeted protein degradation.
Article in Nature chemical biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 238 papers.
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Who cites it
238 citing papers in PubMed, 538 citations in OpenAlex.
- Micellar LYTAC-engineered bionic coatings abrogate RANK-dependent osteocatabolism and boost fibrillogenesis-mimetic mineral accretion for empowering osteoporotic osseointegration.Bioactive materials · 2027Article
- Unlocking the "undruggable": current landscape and emerging frontiers in lysosomal receptor-mediated protein degradation.Drug delivery · 2026Review
- Lysosome-directed targeted protein degradation technologies for overcoming cancer drug resistance: mechanisms, design principles, and therapeutic opportunities.Drug delivery · 2026Review
- Targeted degradation of protein in hematologic malignancies: mechanisms, therapeutic strategies, and clinical prospects.Cancer gene therapy · 2026Review
- Article
- TROP2-Targeting Chimeras (TRTACs) for Tumor Cell-Selective Membrane Protein Degradation and Enhanced Drug Delivery.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Aptamer-Based Heterobifunctional Targeted Degraders in Disease Treatment.Molecules (Basel, Switzerland) · 2026Review
- Targeted Lysosomal Degradation of Extracellular and Membrane Proteins: From Receptor Hijacking to Programmable Endolysosomal Routing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Multiparatopic antibodies overcome tyrosine kinase inhibitor resistance by inducing lysosomal degradation of EGFR mutants.Oncogene · 2026Article
- Synthesis and Biological Evaluation of Well-Defined M6P(n)-Modified Glycopeptides for Targeted Protein Degradation.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Article
- Solute carrier membrane transporters: emerging targets in CNS disorders.Nature reviews. Drug discovery · 2026Review
- Nanotechnology-Enabled Targeted Protein Degradation: Strategies, Opportunities, and Challenges.Small methods · 2026Review
- Engineering Antibodies into Targeted Chimeras: From Recognition Modules to Programmable Degraders.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Design, Synthesis, Biological Studies and Putative Binding Mode of Novel Benzotriazolothalidomide Derivatives as Cereblon Ligands.Chemical biology & drug design · 2026Article
- Towards better outcomes for epidermal growth factor receptor L858R+ lung cancer patients: mutant-selective allosteric inhibitors and the potential for double-drugging.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 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 Plug-and-Play Platform for Customizing Multivalent Degraders and Degrader-Drug Conjugates.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A destination-driven framework for nanoparticle-enabled targeted protein degradation.Acta pharmaceutica Sinica. B · 2026Review
- Review
- A High-Loading Zn Single-Atom Nanozyme Targets the Zn/HIF-1α/GLUT1 Axis to Disrupt Glucose Metabolic Reprogramming and Remodel the Tumor Immune Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
178 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Selective protein degradation platforms have afforded new development opportunities for therapeutics and tools for biological inquiry. The first lysosome-targeting chimeras (LYTACs) targeted extracellular and membrane proteins for degradation by bridging a target protein to the cation-independent mannose-6-phosphate receptor (CI-M6PR). Here, we developed LYTACs that engage the asialoglycoprotein receptor (ASGPR), a liver-specific lysosome-targeting receptor, to degrade extracellular proteins in a cell-type-specific manner. We conjugated binders to a triantenerrary N-acetylgalactosamine (tri-GalNAc) motif that engages ASGPR to drive the downregulation of proteins. Degradation of epidermal growth factor receptor (EGFR) by GalNAc-LYTAC attenuated EGFR signaling compared to inhibition with an antibody. Furthermore, we demonstrated that a LYTAC consisting of a 3.4-kDa peptide binder linked to a tri-GalNAc ligand degrades integrins and reduces cancer cell proliferation. Degradation with a single tri-GalNAc ligand prompted site-specific conjugation on antibody scaffolds, which improved the pharmacokinetic profile of GalNAc-LYTACs in vivo. GalNAc-LYTACs thus represent an avenue for cell-type-restricted protein degradation.
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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.