{
  "abstract": "Several nanomolar galectin-3 inhibitors have advanced to clinical evaluation, which suggests that galectin-3 is a druggable target. These small-molecule inhibitors act by binding to the target protein and rely on an occupancy-driven mode of action that may not fully address intracellular functions of galectin-3. Proteolysis-targeting chimaeras (PROTACs) represent an alternative therapeutic modality, enabling intracellular target depletion with an event-driven mode of action. Galectin-3 is present both intracellularly and extracellularly; however, PROTACs can access only the intracellular pool, raising the question of whether selective intracellular degradation can provide sufficient therapeutic benefit. This perspective examines heterobifunctional galectin-3-targeting molecules composed of a glycomimetic ligand, an E3 ligase-recruiting ligand, and a linker. Their structures, degradation-related data, and mechanisms are critically assessed. Key challenges, including linker optimisation, ligand affinity, and intracellular target accessibility, are discussed. A very recent study demonstrated potent and selective galectin-3 degradation and expanded targeted protein degradation to structurally challenging lectins. Overall, galectin-3 represents a proof-of-principle that galectins undergoing intracellular–extracellular trafficking may potentially be degraded by PROTACs.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ljubljana, Aškerčeva Cesta 7, 1000 Ljubljana, Slovenia"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 1,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Edvin Purić",
      "orcid": "0000-0003-0836-0548"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2x9sayj2z8ysq.bib",
  "cited_by": 0,
  "doi": "10.3390/molecules31213853",
  "fulltext_url": null,
  "id": "2x9sayj2z8ysq",
  "issns": [
    "1420-3049"
  ],
  "landing_url": "https://www.mdpi.com/1420-3049/31/21/3853",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Protein Degradation and Inhibitors"
    ]
  ],
  "openalex": "W7223673696",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-26",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/2x9sayj2z8ysq.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:42Z",
      "native_id": "10.3390/molecules31213853",
      "source": "crossref",
      "url": "https://www.mdpi.com/1420-3049/31/21/3853"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Protein Degradation and Inhibitors",
      "subfield": "molecular-biology"
    }
  ],
  "title": "From Inhibition to Degradation: Can Galectin-3 Be Drugged by Heterobifunctional Degraders?",
  "title_text": "From Inhibition to Degradation: Can Galectin-3 Be Drugged by Heterobifunctional Degraders?",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:42Z",
  "url": "https://research.draconitic.com/paper/2x9sayj2z8ysq",
  "venue": "Molecules",
  "versions": []
}