{
  "abstract": "Cytochrome P450 (CYP) enzymes are heme-thiolate monooxygenases whose inhibition can result from direct reversible axial ligation of the distal heme iron, perturbation of the axial-water environment, or metabolism-dependent heme interactions. This focused review critically examines the chemical classes used as putative heme-binding groups in small-molecule CYP inhibitors, with emphasis on imidazoles, 1,2,4-triazoles, pyridines, 1,2,3-triazoles, sulfur-containing heterocycles, hydroxamates, nitriles and isonitriles. We discuss the evidential limits of ligand-induced type II spectra, distinguish direct parent–ligand coordination from mechanism-based inactivation, and outline an evidence hierarchy integrating enzymology, UV–Vis spectroscopy, EPR-based methods, structural biology and QM/MM calculations. CYP19A1 is used as a medicinal-chemistry case study illustrating how donor identity, binding geometry, scaffold recognition and selectivity against drug-metabolising and steroidogenic CYP enzymes must be optimized concurrently. We propose practical design and validation principles for the development of selectively heme-directed CYP19A1 inhibitors.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Biomedical and Analytical Chemistry, The John Paul II Catholic University of Lublin, St. Konstantynów 1j, 20-708 Lublin, Poland",
    "AI Drug Discovery Center, The John Paul II Catholic University of Lublin, St. Konstantynów 1j, 20-708 Lublin, Poland",
    "Department of Molecular Biology, The John Paul II Catholic University of Lublin, ul. Konstantynów 1i, 20-708 Lublin, Poland"
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Paweł Kozyra",
      "orcid": "0000-0001-8071-8503"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Maciej Masłyk",
      "orcid": "0000-0003-0516-3231"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5khnc7ekjvdtp.bib",
  "cited_by": 0,
  "doi": "10.3390/molecules31203656",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13707629/?tool=EBI",
  "id": "5khnc7ekjvdtp",
  "issns": [
    "1420-3049"
  ],
  "landing_url": "https://www.mdpi.com/1420-3049/31/20/3656",
  "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": [
    [
      "openalex",
      "1604|Metal-Catalyzed Oxygenation Mechanisms"
    ]
  ],
  "openalex": "W7221698766",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13707629/pdf/?tool=EBI",
  "pmcid": "PMC13707629",
  "pmid": null,
  "published": "2026-10-01",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/5khnc7ekjvdtp.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:42Z",
      "native_id": "10.3390/molecules31203656",
      "source": "crossref",
      "url": "https://www.mdpi.com/1420-3049/31/20/3656"
    },
    {
      "first_seen": "2026-10-30T12:21:25Z",
      "native_id": "PMC:PMC13707629",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13707629"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:1604|Metal-Catalyzed Oxygenation Mechanisms",
      "subfield": "inorganic"
    }
  ],
  "title": "Heme-Binding Groups in Cytochrome P450 Inhibitors: Coordination Mechanisms, Evidence Standards and Implications for CYP19A1 Ligand Design",
  "title_text": "Heme-Binding Groups in Cytochrome P450 Inhibitors: Coordination Mechanisms, Evidence Standards and Implications for CYP19A1 Ligand Design",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:25Z",
  "url": "https://research.draconitic.com/paper/5khnc7ekjvdtp",
  "venue": "Molecules",
  "versions": []
}