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September 5, 2025Journal of Medicinal Chemistry

Small-Molecule Ligands Targeting Lysosome-Shuttling Receptors and the Emerging Landscape of Lysosome-Targeting Chimeras

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Authors

JYJingjing YangHZHeping Zhu

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Overview

This Perspective discusses how small-molecule ligands enable targeted protein degradation in lysosome-shuttling receptors, indicating new therapeutic pathways.

Key Points

  • Lysosome-targeting chimeras effectively enhance targeted protein degradation, enabling removal of previously inaccessible extracellular proteins.
  • The study highlights the advantages of small-molecule LYTACs over macromolecular conjugates, including improved pharmacokinetics and tissue penetration.
  • Investigations focus on the structural characteristics and binding mechanisms of ligands interacting with lysosome-shuttling receptors.
  • Future strategies should address challenges to enhance the specificity and translational potential of LYTACs, paving the way for new therapeutic applications.

Cite This Study

Yang et al. (2025) studied this question.

synapsesocial.com/papers/68c239e5b210217d6477e8ffhttps://doi.org/10.1021/acs.jmedchem.5c01019
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Also Consider

Synapse has enriched one closely related paper. Consider it for comparative context:

  1. 1LYMTACs:chimeric small molecules repurpose lysosomal membrane proteins for target protein relocalization and degradation2025 · 13 citations