{
  "abstract": "Degrader–drug conjugates (DDCs) represent an emerging class of therapeutic agents that integrate the mechanism of targeted protein degradation with enhanced drug delivery, offering a promising strategy for precision cancer therapy. We herein report the rational design of GC-C–targeted degrader–drug conjugates (GCCDDCs), a bifunctional modality that promotes selective PD-L1 degradation while concurrently delivering a cytotoxic payload to GC-C–expressing cancer cells. Utilizing the GC-C agonist linaclotide as a targeting moiety, we first engineered GC-C–mediated lysosome-targeting chimeras (GCCTACs), which effectively induced degradation of both extracellular and membranebound proteins in a selective manner. By conjugating a PD-L1-targeting degrader to the microtubule-disrupting agent MMAE, the resulting GCCDDCs exhibit potent antitumor efficacy through coordinated immune checkpoint degradation and direct cytotoxicity. The development of GCCDDCs expands the pharmacological toolbox for targeted protein degraders (TPDs) and X–drug conjugates (XDCs), thereby offering broad utility in chemical",
  "abstract_shown": true,
  "affiliations": [
    "Guangxi Key Laboratory of Chemistry and Engineering of Forest Products",
    "Guangxi Minzu University",
    "Guangdong Key Laboratory of Nanomedicine",
    "Chinese Academy of Sciences",
    "School of Pharmacy",
    "Fudan University"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Yi Zhou"
    },
    {
      "name": "Tengfei Liu"
    },
    {
      "name": "Huaihuai Shi"
    },
    {
      "name": "Xiaozhuo Tan"
    },
    {
      "name": "Hui Pan"
    },
    {
      "name": "Wenyan Dong"
    },
    {
      "name": "Wencong Pan"
    },
    {
      "name": "Jingjing Sun"
    },
    {
      "name": "Wu Su"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Lijing Fang"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Guiyang Yao",
      "orcid": "0000-0001-5730-7597"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/37abezenwr489.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15009517/v1",
  "fulltext_url": null,
  "id": "37abezenwr489",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009517/v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Protein Degradation and Inhibitors"
    ]
  ],
  "openalex": "W7214607515",
  "pdf_url": "https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15009517/v1",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-28",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/37abezenwr489.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:21Z",
      "native_id": "10.26434/chemrxiv.15009517",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009517/v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Protein Degradation and Inhibitors",
      "subfield": "molecular-biology"
    }
  ],
  "title": "GCCDDCs Enable Tumor-Selective Lysosomal Degradation and Payload Delivery via GC-C-Mediated Trafficking",
  "title_text": "GCCDDCs Enable Tumor-Selective Lysosomal Degradation and Payload Delivery via GC-C-Mediated Trafficking",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:21Z",
  "url": "https://research.draconitic.com/paper/37abezenwr489",
  "venue": "ChemRxiv",
  "versions": []
}