ArticleNature chemical biology2021
Bifunctional small molecules that mediate the degradation of extracellular proteins.
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 97 papers, 1 of them a synthesis that pooled it.
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Who cites it
97 citing papers in PubMed, 1 synthesis or guideline pooled it, 218 citations in OpenAlex.
- Emerging protein degradation strategies: expanding the scope to extracellular and membrane proteins.Theranostics · 2021Pooled it
- 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
- TROP2-Targeting Chimeras (TRTACs) for Tumor Cell-Selective Membrane Protein Degradation and Enhanced Drug Delivery.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Synthesis and Biological Evaluation of Well-Defined M6P(n)-Modified Glycopeptides for Targeted Protein Degradation.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Article
- Macropinocytosis-mediated recyclable LYTACs (McR-TACs) for receptor-independent protein degradation.Nature biotechnology · 2026Article
- R17 Drives Heparan Sulfate Clearance via Endolysosomal Trafficking.Israel journal of chemistry · 2026Article
- A nanobody-based proteolysis-targeting chimera offers broad-spectrum protection against diverse influenza virus infections.Signal transduction and targeted therapy · 2026Article
- Molecular engineering of lysosome-based degraders unveils a rapidly expanding therapeutic strategy.Autophagy · 2026Review
- Coacervate-Mediated Lysosome-Targeting Antibody Delivery for Protein Degradation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Potent and Selective IGF-IIR-Recruiting Bifunctional Molecules for Targeted Lysosomal Degradation of Extracellular and Membrane Proteins.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Enzyme-Assisted Synthesis and In Vitro Characterization of Bifunctional PCSK9 Inhibitors.Chembiochem : a European journal of chemical biology · 2026Article
- Extracellular and Membrane Protein: Structure, Biological Functions, Diseases, and an Emerging Modality for Drug Discovery.MedComm · 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
- Induced proximity-based therapeutic modalities.Nature reviews. Drug discovery · 2026Review
- Development of Prostate-Specific Lysosome-Targeting Degraders.Journal of the American Chemical Society · 2026Article
- Targeted Protein Degradation in Cancer: PROTACs, New Targets, and Clinical Mechanisms.Biomolecules · 2026Review
- PSMA-Targeting Chimeras for Cell-Type-Specific Degradation of Surface Immune Checkpoint Protein PD-L1.JACS Au · 2026Article
- Aptamer-Mediated Covalent Dual Lysosome-Targeting Chimeras Enhance Targeted Degradation of Cell Surface Proteins.JACS Au · 2026Article
- Leveraging Targeted Protein Degradation for G Protein-Coupled Receptors: The Development of CCR2 Molecular Degraders.Journal of medicinal chemistry · 2025Article
37 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Targeted protein degradation (TPD) has emerged as a promising therapeutic strategy. Most TPD technologies use the ubiquitin-proteasome system, and are therefore limited to targeting intracellular proteins. To address this limitation, we developed a class of modular, bifunctional synthetic molecules called MoDE-As (molecular degraders of extracellular proteins through the asialoglycoprotein receptor (ASGPR)), which mediate the degradation of extracellular proteins. MoDE-A molecules mediate the formation of a ternary complex between a target protein and ASGPR on hepatocytes. The target protein is then endocytosed and degraded by lysosomal proteases. We demonstrated the modularity of the MoDE-A technology by synthesizing molecules that induce depletion of both antibody and proinflammatory cytokine proteins. These data show experimental evidence that nonproteinogenic, synthetic molecules can enable TPD of extracellular proteins in vitro and in vivo. We believe that TPD mediated by the MoDE-A technology will have widespread applications for disease treatment.
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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.