{
  "abstract": "Antibody-Drug Conjugates (ADCs) have revolutionized targeted cancer therapy, yet their clinical success remains restricted by the limited diversity of cytotoxic payloads. Here we describe the development of verubulin as a novel ADC payload with a dual mechanism of action, combining tubulin inhibition with vascular disruption. Two successive ADC generations were designed and evaluated. First-generation conjugates used amide/carbamate linkage but were hampered by instability and modest efficacy. These limitations were addressed by a quaternarization approach, which delivered stable conjugates with subnanomolar, target-dependent cytotoxicity, and limited bystander activity. In vivo, these ADCs induced tumour regression with excellent tolerability and more durable tumour control than bevacizumab, the clinical reference for vascular disruption, although efficacy remained below benchmark ADCs T-DM1 and T-Dxd. These results support verubulin as a promising payload scaffold for next-generation ADCs.",
  "abstract_shown": true,
  "affiliations": [
    "Faculté de Pharmacie de Strasbourg, Centre National de la Recherche Scientifique/Université de Strasbourg, 74 Route du Rhin, Illkirch-Graffenstaden, France, 67400",
    "ESBS – Pôle API, 300, boulevard Sébastien Brant, CS 10413, Illkirch-Graffenstaden Cedex, France, 67412",
    "UMR7178, Institut pluridisciplinaire Hubert Curien, 23 rue du Lœss, BP 28, Strasbourg Cedex, France, 67037",
    "Nanomedecine laboratory",
    "Institut Strauss"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Héloïse Cahuzac",
      "orcid": "0009-0007-9454-8913"
    },
    {
      "affs": [
        0
      ],
      "name": "Louis Moreira da Silva"
    },
    {
      "affs": [
        0
      ],
      "name": "Yoann Colas"
    },
    {
      "affs": [
        0
      ],
      "name": "Fanny Bousson"
    },
    {
      "affs": [
        0
      ],
      "name": "Caroline Mursch"
    },
    {
      "affs": [
        0
      ],
      "name": "Ketty Pernod"
    },
    {
      "affs": [
        0
      ],
      "name": "Julien Most"
    },
    {
      "affs": [
        1
      ],
      "name": "François Daubeuf"
    },
    {
      "affs": [
        2
      ],
      "name": "Stéphane Erb"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Alexandre Detappe"
    },
    {
      "affs": [
        2
      ],
      "name": "Sarah Cianférani"
    },
    {
      "affs": [
        0
      ],
      "name": "Alain Wagner"
    },
    {
      "affs": [
        0
      ],
      "name": "Guilhem Chaubet"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6h95z0g5n9ww9.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15010926/v1",
  "fulltext_url": null,
  "id": "6h95z0g5n9ww9",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010926/v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2741|Monoclonal and Polyclonal Antibodies Research"
    ]
  ],
  "openalex": "W7223271951",
  "pdf_url": "https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15010926/v1",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-23",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/6h95z0g5n9ww9.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:26Z",
      "native_id": "10.26434/chemrxiv.15010926",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010926/v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2741|Monoclonal and Polyclonal Antibodies Research",
      "subfield": "imaging"
    }
  ],
  "title": "Expanding Antibody-Drug Conjugates Mechanistic Diversity with Verubulin: A Dual Tubulin-Binding and Vascular-Disrupting Payload.",
  "title_text": "Expanding Antibody-Drug Conjugates Mechanistic Diversity with Verubulin: A Dual Tubulin-Binding and Vascular-Disrupting Payload.",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:26Z",
  "url": "https://research.draconitic.com/paper/6h95z0g5n9ww9",
  "venue": "ChemRxiv",
  "versions": []
}