{
  "abstract": "Background: Stevens-Johnson syndrome/toxic epidermal necrolysis, the most acute and severe of severe cutaneous adverse reactions, has an annual incidence of 0.4–13 cases per million and mortality rates range from <10% in Stevens-Johnson syndrome to >40% in toxic epidermal necrolysis, with an overall mortality of approximately 20%. Cyclosporin A (CsA) is clinically effective in Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), but its mechanism beyond calcineurin inhibition remains unclear.\n\nObjectives: To identify novel therapeutic targets of CsA in SJS/TEN using network pharmacology and validate the most promising candidate experimentally.\n\nMethods: Potential CsA targets were predicted using PharmMapper and SuperPred. SJS/TEN-associated genes were retrieved from GeneCards and OMIM. Common targets were analyzed via protein-protein interaction network, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes enrichment. Molecular docking predicted binding modes. The key target interaction was validated in vitro using MicroScale Thermophoresis.\n\nResults: We identified 22 shared targets between CsA and SJS/TEN. Network analysis highlighted five core proteins (MMP9, CASP3, CCL5, CXCR4, CYP3A4). Molecular docking predicted stable binding between CsA and Chemokine (C-C motif) ligand 5 (CCL5). Critically, MST assays demonstrated direct physical interaction between CsA and CCL5 protein with a dissociation constant (Kd) of 2.7 μM.\n\nConclusion: In conclusion, our in vitro experiments confirmed a direct physical binding interaction between CsA and the key chemokine CCL5, providing a novel potential mechanistic hypothesis for the rapid anti-inflammatory effect of CsA in SJS/TEN. However, this hypothesis requires validation through cell-based chemotaxis assays.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Dermatology, Nanchang University Second Affiliated Hospital",
    "Department of Health Toxicology, School of Public Health, Shanxi Medical University"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Fangqin Peng"
    },
    {
      "affs": [
        1
      ],
      "name": "Wenjie Hao"
    },
    {
      "affs": [
        0
      ],
      "name": "Yating Peng"
    },
    {
      "affs": [
        0
      ],
      "name": "Ougen Liu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fk1sjq559fh0f.bib",
  "cited_by": 0,
  "doi": "10.3389/fphar.2026.1853184",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13731316/",
  "id": "fk1sjq559fh0f",
  "issns": [
    "1663-9812"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1853184/full",
  "language": "en",
  "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": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "2736|Drug-Induced Adverse Reactions"
    ]
  ],
  "openalex": "W7223088914",
  "pdf_url": "https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2026.1853184/pdf",
  "pmcid": "PMC13731316",
  "pmid": "42984874",
  "published": "2026-10-21",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/fk1sjq559fh0f.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:06Z",
      "native_id": "10.3389/fphar.2026.1853184",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1853184/full"
    },
    {
      "first_seen": "2026-11-08T12:21:32Z",
      "native_id": "PMC13731316",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fphar.2026.1853184"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2736|Drug-Induced Adverse Reactions",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Cyclosporin a directly binds CCL5: a novel mechanism in SJS/TEN revealed by network pharmacology",
  "title_text": "Cyclosporin a directly binds CCL5: a novel mechanism in SJS/TEN revealed by network pharmacology",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:21:32Z",
  "url": "https://research.draconitic.com/paper/fk1sjq559fh0f",
  "venue": "Frontiers in Pharmacology",
  "versions": []
}