{
  "abstract": "Sepsis is a leading cause of mortality among patients in intensive care units (ICUs), with no specific treatments for sepsis available in clinical practice. In this study, we report the discovery of compound A12, a tanshinone derivative featuring a covalent warhead, which demonstrates potent anti-inflammatory effects both in vitro and in vivo. In a lipopolysaccharide-induced mouse model of endotoxemia and acute systemic inflammation, A12 significantly reduces levels of TNF-α, IL-6, and IL-12. Distinct from current anti-inflammatory small molecules, A12 presents a unique mechanism, covalently binding to DNAJC9, thereby modulating the HSP complex and inhibiting the downstream inflammatory response. This work represents the first application of covalent drug design principles to the structural modification of the natural product tanshinone, and reveals the previously unrecognized role of DNAJC9 in inflammatory diseases, offering a novel therapeutic target for management of sepsis-associated acute systemic inflammation.",
  "abstract_shown": true,
  "affiliations": [
    "State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.",
    "State Key Laboratory of Chemical Biology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.",
    "University of Chinese Academy of Sciences, Beijing 100049, China.",
    "School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China.",
    "School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China.",
    "Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.",
    "Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Institute of Clinical Pharmacology, Anhui Medical University, Hefei 230032, China.",
    "Lingang Laboratory, Shanghai 200031, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Xingjun Li"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Tao Yang"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Hui Huang"
    },
    {
      "affs": [
        1,
        4
      ],
      "name": "Yalan Ma"
    },
    {
      "affs": [
        0,
        5
      ],
      "name": "Lu Liu"
    },
    {
      "affs": [
        6
      ],
      "name": "Qingqing Li"
    },
    {
      "affs": [
        1,
        4
      ],
      "name": "Naixia Zhang"
    },
    {
      "affs": [
        4
      ],
      "name": "Zhizhen Hui"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Yazhou Li"
    },
    {
      "affs": [
        5
      ],
      "name": "Fang Bai"
    },
    {
      "affs": [
        4
      ],
      "name": "Qiangqiang Chen"
    },
    {
      "affs": [
        0,
        7
      ],
      "name": "Jiang Wang"
    },
    {
      "affs": [
        1
      ],
      "name": "Chen Zhou"
    },
    {
      "affs": [
        0,
        2,
        3
      ],
      "name": "Hu Zhou"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Wei Tang"
    },
    {
      "affs": [
        0,
        2,
        3,
        4,
        5
      ],
      "name": "Hong Liu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cwbhqbh8y2nn7.bib",
  "cited_by": 0,
  "doi": "10.1016/j.apsb.2026.06.042",
  "fulltext_url": "https://europepmc.org/articles/PMC13712289",
  "id": "cwbhqbh8y2nn7",
  "issns": [
    "2211-3835",
    "2211-3843"
  ],
  "landing_url": "https://europepmc.org/article/MED/42948689",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Article"
    ],
    [
      "openalex",
      "2713|Sepsis Diagnosis and Treatment"
    ]
  ],
  "openalex": "W7165795260",
  "pdf_url": "https://europepmc.org/articles/PMC13712289?pdf=render",
  "pmcid": "PMC13712289",
  "pmid": "42948689",
  "published": "2026-06-24",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/cwbhqbh8y2nn7.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:20:36Z",
      "native_id": "MED:42948689",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42948689"
    },
    {
      "first_seen": "2026-10-31T12:22:54Z",
      "native_id": "PMC13712289",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.apsb.2026.06.042"
    }
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2713|Sepsis Diagnosis and Treatment",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Discovery of a potent covalent inhibitor for the treatment of sepsis targeting DNAJC9: Identification of a druggable target for inflammation.",
  "title_text": "Discovery of a potent covalent inhibitor for the treatment of sepsis targeting DNAJC9: Identification of a druggable target for inflammation.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:22:54Z",
  "url": "https://research.draconitic.com/paper/cwbhqbh8y2nn7",
  "venue": "Acta pharmaceutica Sinica. B",
  "versions": []
}