{
  "abstract": "Regnase-1 is an essential RNase that suppresses immune cell activation by targeting the mRNA of pro-inflammatory cytokines such as interleukin 6 (IL-6). Although genetic inhibition of Regnase-1 activity in CD8+ T cells has been shown to enhance antitumor immunity, no molecular inhibitors of Regnase-1 have been reported. By exploiting a library of nucleic acid analogs in conjunction with an RNA displacement assay, we identified multiple candidate competitors of Regnase-1 RNA substrates. Among these, suramin-an approved drug for treating African sleeping sickness-and several of its derivatives displaced Regnase-1 RNA targets with submicromolar affinity, competitively inhibited Regnase-1-mediated degradation of RNA in vitro, and enhanced Il6 mRNA levels and IL-6 production in mouse embryonic fibroblasts. A 2.62 Å crystal structure revealed that suramin bound to the Regnase-1 active site, coordinating with the catalytic Mg²⁺. Quantum chemical calculations further elucidated qualitative interactions between suramin and surrounding residues of Regnase-1. These findings establish suramin as a small-molecule inhibitor of Regnase-1-mediated RNA decay.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Genome Informatics, Research Institute for Microbial Diseases (RIMD), The University of Osaka, 565-0871Osaka, Japan.",
    "Laboratory for Systems Immunology, Immunology Frontier Research Center (WPI-iFReC), The University of Osaka, 565-0871Osaka, Japan.",
    "Laboratory of Host Defense, WPI-iFReC, The University of Osaka, 565-0871Osaka, Japan.",
    "TechnoPro, Inc. TechnoPro R&D, Company, 650-0047Kobe, Japan.",
    "Protein Crystallography Laboratory, Institute for Protein Research, The University of Osaka, 565-0871Osaka, Japan.",
    "Graduate School of Pharmaceutical Sciences, The University of Osaka, 565-0871Osaka, Japan.",
    "Department of Chemistry, Kunsan National University, 54150Gunsan, Republic of Korea.",
    "Department of Host Defense, RIMD, The University of Osaka, 565-0871Osaka, Japan.",
    "Center for Advanced Modalities and Drug Delivery System (CAMaD), The University of Osaka, 565-0871Osaka, Japan."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Arthur Millius",
      "orcid": "0000-0002-5280-6730"
    },
    {
      "affs": [
        0
      ],
      "name": "Chee-Hong Takahiro Yew",
      "orcid": "0000-0002-8735-0665"
    },
    {
      "affs": [
        3
      ],
      "name": "Yuko Misumi"
    },
    {
      "affs": [
        4
      ],
      "name": "Jian Yu",
      "orcid": "0000-0003-2854-9225"
    },
    {
      "affs": [
        5
      ],
      "name": "Daisuke Takaya",
      "orcid": "0000-0001-6020-8151"
    },
    {
      "affs": [
        5
      ],
      "name": "Shuhei Miyakawa",
      "orcid": "0009-0005-6275-5550"
    },
    {
      "affs": [
        6
      ],
      "name": "Eun-Sol Choi"
    },
    {
      "affs": [
        6
      ],
      "name": "Hyo-Jun Lee",
      "orcid": "0000-0001-6790-5160"
    },
    {
      "affs": [
        0
      ],
      "name": "Tatum Melati Andini",
      "orcid": "0009-0001-7865-2506"
    },
    {
      "affs": [
        0
      ],
      "name": "Fahad Khalaf",
      "orcid": "0009-0009-3677-8774"
    },
    {
      "affs": [
        2,
        7
      ],
      "name": "Kazuhiko Maeda",
      "orcid": "0000-0003-0305-8163"
    },
    {
      "affs": [
        5
      ],
      "name": "Kaori Fukuzawa",
      "orcid": "0000-0001-5357-8250"
    },
    {
      "affs": [
        4
      ],
      "name": "Genji Kurisu",
      "orcid": "0000-0002-5354-0807"
    },
    {
      "affs": [
        2,
        7,
        8
      ],
      "name": "Shizuo Akira",
      "orcid": "0000-0001-7602-9617"
    },
    {
      "affs": [
        1
      ],
      "name": "Soyoung Park",
      "orcid": "0000-0001-7855-1302"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Daron M Standley",
      "orcid": "0000-0003-4078-0817"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/64j01k7770ahn.bib",
  "cited_by": 0,
  "doi": "10.1093/narmme/ugag043",
  "fulltext_url": "https://europepmc.org/articles/PMC13684271",
  "id": "64j01k7770ahn",
  "issns": [
    "2976-856X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42909357",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|RNA Research and Splicing"
    ]
  ],
  "openalex": "W7215074242",
  "pdf_url": "https://europepmc.org/articles/PMC13684271?pdf=render",
  "pmcid": "PMC13684271",
  "pmid": "42909357",
  "published": "2026-10-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/64j01k7770ahn.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:14Z",
      "native_id": "MED:42909357",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42909357"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|RNA Research and Splicing",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Identification of small-molecule inhibitors of the immune system repressor Regnase-1.",
  "title_text": "Identification of small-molecule inhibitors of the immune system repressor Regnase-1.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:14Z",
  "url": "https://research.draconitic.com/paper/64j01k7770ahn",
  "venue": "NAR molecular medicine",
  "versions": []
}