{
  "abstract": "Inhibitor of Apoptosis Proteins (IAPs) are key regulators of tumor progression, invasiveness, and chemoresistance, and their contribution varies across different tumor types. Here, we evaluated an expanded library of benzodiazepinone derivatives in invasive and chemoresistant human cancer cell lines (MDA-MB-231, BT-549, NCI-H1299, and PC-3), in which IAP-dependent signaling has been implicated to different extents. These compounds were developed from a parental benzodiazepinone previously shown to bind IAPs in vitro using isolated proteins and to target IAPs in MDA-MB-231 cells. The expanded library retained cytotoxic activity beyond MDA-MB-231 cells, extending to BT-549 and NCI-H1299, whereas limited effect was observed in PC-3 cells. Tumor Necrosis Factor (TNFα) co-treatment further enhanced the cytotoxic activity of selected derivatives, although the magnitude of this effect differed among cell lines, suggesting a differential contribution of TNFα/NF-κB (Nuclear Factor kappa-light-chain-enhancer of activated B cells) signaling, potentially involving IAP regulated pathway. Overall, these findings expand the biological profile of this benzodiazepinone scaffold and support its further investigation as a promising lead for the development of therapies against aggressive and chemoresistant cancers.",
  "abstract_shown": true,
  "affiliations": [
    "Institute of Biophysics-National Research Council (IBF-CNR) Genoa Unit, via De Marini, 6, 16149 Genoa, Italy",
    "Department of Experimental Medicine, Section of Biochemistry, University of Genoa, Viale Benedetto XV 1, 16132 Genoa, Italy",
    "Institute of Biophysics-National Research Council (IBF-CNR) Milan Unit, Via Corti 12, 20133 Milano, Italy",
    "Department of Pharmacy, Section of Medicinal Chemistry, School of Medical and Pharmaceutical Sciences, University of Genoa, Viale Benedetto XV, 3, 16132 Genoa, Italy"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Michele Fiore",
      "orcid": "0000-0002-6489-2648"
    },
    {
      "affs": [
        1
      ],
      "name": "Dario Lunaccio"
    },
    {
      "affs": [
        2
      ],
      "name": "Elisa Fagnani",
      "orcid": "0009-0002-8764-2710"
    },
    {
      "affs": [
        2
      ],
      "name": "Paolo Cocomazzi",
      "orcid": "0000-0003-4733-6428"
    },
    {
      "affs": [
        2
      ],
      "name": "Francesco Bonì"
    },
    {
      "affs": [
        3
      ],
      "name": "Bruno Tasso",
      "orcid": "0000-0002-5636-5645"
    },
    {
      "affs": [
        1
      ],
      "name": "Annalisa Salis",
      "orcid": "0000-0002-3082-2908"
    },
    {
      "affs": [
        1
      ],
      "name": "Enrico Millo",
      "orcid": "0000-0002-4019-0051"
    },
    {
      "affs": [
        2
      ],
      "name": "Federica Cossu",
      "orcid": "0000-0001-9753-3572"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/17kz30sc4x1j3.bib",
  "cited_by": 0,
  "doi": "10.3390/molecules31214016",
  "fulltext_url": null,
  "id": "17kz30sc4x1j3",
  "issns": [
    "1420-3049"
  ],
  "landing_url": "https://www.mdpi.com/1420-3049/31/21/4016",
  "language": null,
  "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": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-07",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/17kz30sc4x1j3.ris",
  "sources": [
    {
      "first_seen": "2026-11-10T00:21:21Z",
      "native_id": "10.3390/molecules31214016",
      "source": "crossref",
      "url": "https://www.mdpi.com/1420-3049/31/21/4016"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "issn:1420-3049",
      "subfield": "general"
    }
  ],
  "title": "Tumor-Dependent Cytotoxicity of Novel Benzodiazepinones Across Cancers with Distinct IAP-Associated Aggressiveness",
  "title_text": "Tumor-Dependent Cytotoxicity of Novel Benzodiazepinones Across Cancers with Distinct IAP-Associated Aggressiveness",
  "type": "peer-reviewed",
  "updated_at": "2026-11-10T00:21:21Z",
  "url": "https://research.draconitic.com/paper/17kz30sc4x1j3",
  "venue": "Molecules",
  "versions": []
}