{
  "abstract": "The gadolinium-conjugated diflunisal derivative ETN102 has previously been shown to suppress cyclooxygenase-2 (COX-2) levels, reduce glial activation, and attenuate neuronal damage associated with stroke. In the present study, we investigated whether ETN102 modulates platelet aggregation and activation. ETN102 selectively inhibited thrombin-induced platelet aggregation while sparing platelet responses to other agonists, including collagen, adenosine diphosphate (ADP), and U46619. ETN102 also reduced adenosine triphosphate (ATP) secretion under aggregating conditions without altering thromboxane B ₂ (TXB ₂ ) generation, suggesting that its antiplatelet effect is independent of the COX-1-dependent thromboxane signaling. Flow cytometric and biochemical analyses further demonstrated that ETN102 suppressed thrombin-induced αIIbβ3 integrin activation, platelet spreading, clot retraction, and the phosphorylation of focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (Pyk2), without affecting granule secretion, intracellular Ca ²⁺ mobilization, or phosphorylation of Syk, PI3K, and AKT signaling molecules. In vivo , ETN102 significantly prolonged carotid artery occlusion time in a ferric chloride (FeCl ₃ )-induced thrombosis model and increased tail bleeding time and hemoglobin content. In addition, ETN102 reduced infarct volume and improved neuronal survival markers in a murine model of cerebral ischemia/reperfusion injury. These findings demonstrate that ETN102 is a thrombin-context selective modulator of platelet integrin αIIbβ3 outside-in signaling, with antithrombotic and neuroprotective potential.",
  "abstract_shown": true,
  "affiliations": [
    "Korean Medicine-Application Center, Korea Institute of Oriental Medicine",
    "Korean Convergence Medical Science Major, KIOM School, University of Science and Technology (UST)",
    "Department of R & D Center, Etnova Therapeutics Corp."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Malk Eun Pak"
    },
    {
      "affs": [
        0
      ],
      "name": "Yeon-Ji Kim"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Hado Choi"
    },
    {
      "affs": [
        2
      ],
      "name": "Garam Choi"
    },
    {
      "affs": [
        2
      ],
      "name": "Yeoun-Hee Kim"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Kyungho Kim"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bw1ahfz0xe4pp.bib",
  "cited_by": 0,
  "doi": "10.3389/fphar.2026.1936307",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13725699/?tool=EBI",
  "id": "bw1ahfz0xe4pp",
  "issns": [
    "1663-9812"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1936307/full",
  "language": "eng",
  "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",
      "2720|Platelet Disorders and Treatments"
    ]
  ],
  "openalex": "W7222941227",
  "pdf_url": "https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2026.1936307/pdf",
  "pmcid": "PMC13725699",
  "pmid": "42973918",
  "published": "2026-10-19",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/bw1ahfz0xe4pp.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:06Z",
      "native_id": "10.3389/fphar.2026.1936307",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1936307/full"
    },
    {
      "first_seen": "2026-11-03T15:20:51Z",
      "native_id": "PMC:PMC13725699",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13725699"
    },
    {
      "first_seen": "2026-11-04T12:24:00Z",
      "native_id": "PMC13725699",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fphar.2026.1936307"
    },
    {
      "first_seen": "2026-11-04T15:20:48Z",
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      "url": "https://europepmc.org/article/MED/42973918"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "issn:1663-9812",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "The inhibitory effect of gadolinium-conjugated diflunisal on platelet function through regulating outside-in signaling of αIIbβ3 integrin",
  "title_text": "The inhibitory effect of gadolinium-conjugated diflunisal on platelet function through regulating outside-in signaling of αIIbβ3 integrin",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T12:22:12Z",
  "url": "https://research.draconitic.com/paper/bw1ahfz0xe4pp",
  "venue": "Frontiers in Pharmacology",
  "versions": []
}