{
  "abstract": "The classical estrogen receptor (ER) is a steroid hormone receptor known for its role in both health and disease. ER, like its counterpart ER{beta}, acts as a receptor for its endogenous ligand 17{beta}-estradiol (E2) and is capable of binding a diverse set of natural and synthetic small molecules. Several screening campaigns have identified various ER ligands, based on the oxabicyclo[3.3.1]-nonene scaffold, that act as ER agonists. One such campaign extensively characterized an oxabicyclic ER agonist, termed AB-1. Herein, we report the synthesis of a series of analogs based on the scaffold of AB-1 (herein termed 1), focusing on the enhancement of their binding to ER and functional potencies in ER mediated assays. We identify a new substituted compound 9 that achieves subnanomolar potencies for ER binding (IC50= 0.45 nM) and ER dependent transcription (EC50= 0.37 nM) and proliferation (EC50= 0.03 nM), with potencies approaching those of E2. The high potency of 9 provides a promising scaffold for the potential development of new ER-targeted therapeutics.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Internal Medicine, Division of Molecular Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131, USA"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "name": "R. A. Pepermans"
    },
    {
      "name": "A. J. Tenorio"
    },
    {
      "name": "T. Saxon"
    },
    {
      "name": "M. R. Talipov"
    },
    {
      "name": "W. A. Maio"
    },
    {
      "name": "C. Ramesh"
    },
    {
      "affs": [
        0
      ],
      "name": "E. R. Prossnitz"
    },
    {
      "name": "J. B. Arterburn"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/a0g57g9csdfnp.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.25.754525",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.25.754525v1.full",
  "id": "a0g57g9csdfnp",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.25.754525v1",
  "language": null,
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "pharmacology and toxicology"
    ],
    [
      "openalex",
      "1311|Estrogen and related hormone effects"
    ]
  ],
  "openalex": "W7215121367",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.25.754525v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-25",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/a0g57g9csdfnp.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:25:41Z",
      "native_id": "10.64898/2026.09.25.754525",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.25.754525v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:pharmacology and toxicology",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Synthesis of substituted oxabicyclic phenol derivatives with increased affinity and activity for the classical estrogen receptor ERα",
  "title_text": "Synthesis of substituted oxabicyclic phenol derivatives with increased affinity and activity for the classical estrogen receptor ERα",
  "type": "preprint",
  "updated_at": "2026-10-30T12:25:41Z",
  "url": "https://research.draconitic.com/paper/a0g57g9csdfnp",
  "venue": "bioRxiv",
  "versions": []
}