{
  "id": 11333895,
  "title": "Synthesis of substituted oxabicyclic phenol derivatives with increased affinity and activity for the classical estrogen receptor ERα",
  "url": "https://urgent.news/2026/10/01/synthesis-of-substituted-oxabicyclic-phenol-derivatives-with",
  "topic": "science",
  "section": "Science",
  "published": "2026-10-01T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.09.25.754525v1?rss=1"
  },
  "original_language": "en",
  "account": "The classical estrogen receptor (ER) plays a crucial role in health and disease, acting as a receptor for its endogenous ligand 17β-estradiol (E2). Like its counterpart ERβ, ER can bind a wide range of natural and synthetic small molecules. Extensive screening efforts have led to the discovery of various ER agonists, many of which are based on the oxabicyclo[3.3.1]-nonene scaffold. One such compound, AB-1, was the focus of a detailed investigation.\n\nThe study details the synthesis of a series of analogs derived from the AB-1 scaffold, with the aim of enhancing their binding affinity to the ER and improving their functional potencies in ER-mediated assays. Among these analogs, compound 9 stands out for its remarkable properties. Compound 9 exhibits subnanomolar potencies for ER binding, with an IC50 value of just 0.45 nM. This potency also extends to ER-dependent transcription, with an EC50 of 0.37 nM, and ER-mediated cell proliferation, with an EC50 of 0.03 nM. Such high potencies are remarkably close to those of the endogenous ligand E2, indicating that compound 9 could be a promising scaffold for the development of new ER-targeted therapeutics.",
  "summary": "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…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}