{
  "abstract": "Molecules that form irreversible covalent bonds with their targets are a mainstay of drug discovery and chemical biology research. Their ability to permanently inactivate an enzyme target provides a mechanism with significant potential to modulate disease phenotypes. This perspective discusses the trajectory of the field of irreversible enzyme inhibitors with an outlook on emerging methods, warhead structures, and sentiments presently directing practices in the discovery and design of the next wave of covalent agents.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Medicinal Chemistry, Institute for Biomedical Engineering, Faculty of Medicine, Eberhard Karls Universität Tübingen, Tübingen72076, Germany.",
    "Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmaceutical Sciences, Eberhard Karls Universität Tübingen, Tübingen72076, Germany.",
    "Cluster of Excellence iFIT (EXC 2180) \"Image-Guided and Functionally Instructed Tumor Therapies\" Eberhard Karls Universität Tübingen, Tübingen72076, Germany.",
    "Department of Chemistry, College of Arts and Sciences, The State University of New York at Buffalo, Buffalo, New York14260, United States.",
    "Department of Structural Biology, Jacobs School of Medicine and Biomedical Sciences, Buffalo, New York14203, United States.",
    "Department of Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, New York14214, United States.",
    "Department of Pharmacology and Therapeutics, , Roswell Park Comprehensive Cancer Center, Buffalo, New York14203, United States."
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Matthias Gehringer",
      "orcid": "0000-0003-0163-3419"
    },
    {
      "affs": [
        3,
        4,
        5,
        6
      ],
      "name": "David E Heppner",
      "orcid": "0000-0002-0722-5160"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/aakn8xyn40rhr.bib",
  "cited_by": 0,
  "doi": "10.1021/acs.biochem.6c00624",
  "fulltext_url": "https://europepmc.org/articles/PMC13689819",
  "id": "aakn8xyn40rhr",
  "issns": [
    "0006-2960",
    "1520-4995"
  ],
  "landing_url": "https://europepmc.org/article/MED/42899594",
  "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",
      "1605|Click Chemistry and Applications"
    ]
  ],
  "openalex": "W7220360186",
  "pdf_url": "https://europepmc.org/articles/PMC13689819?pdf=render",
  "pmcid": "PMC13689819",
  "pmid": "42899594",
  "published": "2026-10-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/aakn8xyn40rhr.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:37Z",
      "native_id": "MED:42899594",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42899594"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:1605|Click Chemistry and Applications",
      "subfield": "organic"
    }
  ],
  "title": "In Pursuit of Enduring Inactivation: A Perspective on the Development and Study of Irreversible-Covalent Inhibitors.",
  "title_text": "In Pursuit of Enduring Inactivation: A Perspective on the Development and Study of Irreversible-Covalent Inhibitors.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:37Z",
  "url": "https://research.draconitic.com/paper/aakn8xyn40rhr",
  "venue": "Biochemistry",
  "versions": []
}