{
  "abstract": "Succinate dehydrogenase (SDH, complex II) connects the tricarboxylic acid (TCA) cycle to the electron transport chain (ETC), maintaining mitochondrial energy homeostasis. Selective SDH inhibition in diseased tissue has remained challenging due to the highly conserved catalytic architecture across normal tissues. Here, we reveal that SDH catalytic activity depends on the acetylation state of its catalytic subunit A (SDHA): the non‐acetylated form is catalytically active but exhibits fragile homeostasis in bladder cancer, contrasting with its robust maintenance in normal cells. Guided by this insight, we designed ZPI‐3, a conformationally optimized inhibitor that selectively engages the non‐acetylated SDHA, suppressing tumor SDH activity and growth while sparing normal cells. In orthotopic NMIBC models, ZPI‐3 outperforms mitomycin‐C. Differential SDH responses to ZPI‐3 in clinical specimens further suggest its potential for patient stratification and precision therapy. These findings establish modification‐selective inhibition as a paradigm for tumor‐selective mitochondrial modulation.",
  "abstract_shown": true,
  "affiliations": [
    "College of Chemistry and Materials Science Jiangsu Key Laboratory of Bio‐functional Materials Jiangsu Collaborative Innovation Centre of Biomedical Functional Materials Nanjing Normal University Nanjing China",
    "School of Science Key Laboratory of High Performance Scientific Computation Xihua University Chengdu China",
    "Department of Urology Nanjing Drum Tower Hospital the Affiliated Hospital of Nanjing University Medical School Institute of Urology Nanjing University Nanjing China",
    "School of Chemistry and Chemical Engineering Yancheng Institute of Technology Yancheng China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Kaikai Xu"
    },
    {
      "affs": [
        0
      ],
      "name": "Lulu Kong"
    },
    {
      "affs": [
        0
      ],
      "name": "Kebin Ye"
    },
    {
      "affs": [
        0
      ],
      "name": "Xinlu Bao"
    },
    {
      "affs": [
        0
      ],
      "name": "Haowen Liu"
    },
    {
      "affs": [
        1
      ],
      "name": "Ning Wang",
      "orcid": "0000-0002-9515-308X"
    },
    {
      "affs": [
        2
      ],
      "name": "Yongming Deng",
      "orcid": "0009-0004-3571-2427"
    },
    {
      "affs": [
        3
      ],
      "name": "Wei Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Shaohua Wei"
    },
    {
      "affs": [
        0
      ],
      "name": "Lin Zhou",
      "orcid": "0000-0003-3836-3782"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2esxc82tn8jjj.bib",
  "cited_by": 0,
  "doi": "10.1002/advs.77046",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13487864/",
  "id": "2esxc82tn8jjj",
  "issns": [
    "2198-3844"
  ],
  "landing_url": "https://doi.org/10.1002/advs.77046",
  "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",
      "Research Article"
    ],
    [
      "openalex",
      "1306|Cancer, Hypoxia, and Metabolism"
    ]
  ],
  "openalex": "W7203772576",
  "pdf_url": null,
  "pmcid": "PMC13487864",
  "pmid": "42615355",
  "published": "2026-08-19",
  "publisher": "Wiley",
  "ris": "https://research.draconitic.com/paper/2esxc82tn8jjj.ris",
  "sources": [
    {
      "first_seen": "2026-11-11T12:22:35Z",
      "native_id": "PMC13487864",
      "source": "pmc",
      "url": "https://doi.org/10.1002/advs.77046"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:1306|Cancer, Hypoxia, and Metabolism",
      "subfield": "oncology"
    }
  ],
  "title": "Modification‐Selective Inhibition of Succinate Dehydrogenase a Enables Tumor‐Restricted Mitochondrial Modulation",
  "title_text": "Modification‐Selective Inhibition of Succinate Dehydrogenase a Enables Tumor‐Restricted Mitochondrial Modulation",
  "type": "peer-reviewed",
  "updated_at": "2026-11-13T12:20:17Z",
  "url": "https://research.draconitic.com/paper/2esxc82tn8jjj",
  "venue": "Advanced Science",
  "versions": []
}