{
  "abstract": "Proteolysis-targeting chimeras (PROTACs) represent an emerging therapeutic modality that harnesses the ubiquitin-proteasome system to induce targeted protein degradation (TPD). Their event-driven and catalytic mechanisms provide new opportunities to target previously undruggable proteins. However, the rapid expansion of TPD technologies, including molecular glues (MGs) and X-functional targeting chimeras (XTACs), together with the increasing application of artificial intelligence (AI) in degrader design, highlights the need for comprehensive and continuously updated data resources. Here, we present PROTAC-DB 4.0, an expanded knowledgebase covering major targeted degradation and induced-proximity technologies. Compared with the previous version, PROTAC-DB 4.0 contains 15 502 PROTAC entries, together with 24 798 MG entries and 272 XTAC entries, with expanded experimental annotations, patent-derived compounds, and modality-specific data fields. A major advancement in PROTAC-DB 4.0 is the integration of a large language model and retrieval-augmented generation-based natural language query system, which connects structured database records with scientific literature to enable intuitive knowledge discovery across PROTACs, MGs, and XTACs. By combining comprehensive data curation with AI-assisted information retrieval, PROTAC-DB 4.0 provides an accessible platform to support degrader discovery, data-driven modeling, and rational design of next-generation targeted degradation and induced-proximity therapeutics. PROTAC-DB 4.0 is freely accessible at http://cadd.zju.edu.cn/protacdb/.",
  "abstract_shown": true,
  "affiliations": [
    "College of Pharmaceutical Sciences, Zhejiang University , Hangzhou 310058 Zhejiang ,",
    "CarbonSilicon AI Technology Company, Ltd. , Hangzhou 310018 Zhejiang ,",
    "Department of Medicinal Chemistry, China Pharmaceutical University , Nanjing 210009 Jiangsu ,",
    "Innovation Center for AI and Drug Discovery, School of Pharmacy, East China Normal University , Shanghai 200062 ,",
    "Vollum Institute, Oregon Health and Science University , Portland, OR 97239 ,",
    "College of Computer Science and Technology, Zhejiang University-University of Illinois Urbana-Champaign Institute, Zhejiang University , Hangzhou, Zhejiang 310027 ,",
    "State Key Laboratory of Transvascular Implantation Devices of The Second Affiliated Hospital, School of Medicine and School of Public Health, Zhejiang University , Hangzhou 310003 ,"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Jingxuan Ge"
    },
    {
      "affs": [
        2
      ],
      "name": "Chen Yin"
    },
    {
      "affs": [
        0
      ],
      "name": "Yurong Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Shi Li"
    },
    {
      "affs": [
        2
      ],
      "name": "Kexin Xu"
    },
    {
      "affs": [
        3
      ],
      "name": "Rongfan Tang"
    },
    {
      "affs": [
        4
      ],
      "name": "Gaoqi Weng"
    },
    {
      "affs": [
        1
      ],
      "name": "Hao Luo"
    },
    {
      "affs": [
        0
      ],
      "name": "Lin Tang"
    },
    {
      "affs": [
        0
      ],
      "name": "Youqiao Qian"
    },
    {
      "affs": [
        0
      ],
      "name": "Shukai Gu"
    },
    {
      "affs": [
        0
      ],
      "name": "Chang-Yu Hsieh",
      "orcid": "0000-0002-6242-4218"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Jian Wu"
    },
    {
      "affs": [
        0
      ],
      "name": "Dan Li"
    },
    {
      "affs": [
        2
      ],
      "name": "Huiyong Sun",
      "orcid": "0000-0002-7107-7481"
    },
    {
      "affs": [
        0
      ],
      "name": "Tingjun Hou",
      "orcid": "0000-0001-7227-2580"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2jdsdhwr57gnh.bib",
  "cited_by": 0,
  "doi": "10.1093/nar/gkag1098",
  "fulltext_url": null,
  "id": "2jdsdhwr57gnh",
  "issns": [
    "0305-1048",
    "1362-4962"
  ],
  "landing_url": "https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkag1098/9005752",
  "language": null,
  "licence": "CC-BY-NC-4.0",
  "licence_label": "CC BY-NC 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [],
  "openalex": null,
  "pdf_url": "https://academic.oup.com/nar/advance-article-pdf/doi/10.1093/nar/gkag1098/72639794/gkag1098.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-31",
  "publisher": "Oxford University Press (OUP)",
  "ris": "https://research.draconitic.com/paper/2jdsdhwr57gnh.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:21:18Z",
      "native_id": "10.1093/nar/gkag1098",
      "source": "crossref",
      "url": "https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkag1098/9005752"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "issn:0305-1048",
      "subfield": "molecular-biology"
    }
  ],
  "title": "PROTAC-DB 4.0: an expanded knowledgebase of targeted protein degradation modalities with AI-powered knowledge discovery",
  "title_text": "PROTAC-DB 4.0: an expanded knowledgebase of targeted protein degradation modalities with AI-powered knowledge discovery",
  "type": "peer-reviewed",
  "updated_at": "2026-11-02T00:21:29Z",
  "url": "https://research.draconitic.com/paper/2jdsdhwr57gnh",
  "venue": "Nucleic Acids Research",
  "versions": []
}