{
  "abstract": "Interest in the P2Y6 receptor (P2Y6R) has increased substantially over the past decade, driven by evidence that pharmacological inhibition is beneficial in neurodegenerative disease models, inflammatory pathologies, and cancer. However, therapeutic targeting of the P2Y6R has remained a challenge due to a lack of available drug-like molecules. In 2023 and 2024, benzimidazole and quinoline chemotypes respectively, were reported as potent P2Y6R antagonists with pharmacological relevance in an inflammatory bowel disease model. In the present study positive and negative controls from each chemotype were selected, and their functional activity at hP2Y6R was assessed prior to chemical diversification. Contrary to the published literature, none of the antagonists exhibited functional activity in our Ca²⁺ mobilisation assay reported herein. These findings emphasise the ongoing challenges in reliably assessing pharmacological activity at the hP2Y6R and highlight a key barrier to progression of the field.",
  "abstract_shown": true,
  "affiliations": [
    "School of Chemistry, Faculty of Science, University of Sydney, Sydney, NSW, 2006, Australia.",
    "Sydney Pharmacy School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, 2006, Australia.",
    "School of Chemistry, Faculty of Science, University of Sydney, Sydney, NSW, 2006, Australia. michael.kassiou@sydney.edu.au."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Chianna Dane",
      "orcid": "0009-0001-3730-9453"
    },
    {
      "affs": [
        0
      ],
      "name": "André D J McKenzie",
      "orcid": "0000-0002-8012-4745"
    },
    {
      "affs": [
        0
      ],
      "name": "Andrew P Montgomery",
      "orcid": "0000-0002-1819-3619"
    },
    {
      "affs": [
        1
      ],
      "name": "Jonathan Du",
      "orcid": "0000-0002-7750-4413"
    },
    {
      "affs": [
        0
      ],
      "name": "Eryn L Werry",
      "orcid": "0000-0002-6224-1286"
    },
    {
      "affs": [
        2
      ],
      "name": "Michael Kassiou",
      "orcid": "0000-0002-6655-0529"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1ah2f4xtjne37.bib",
  "cited_by": 0,
  "doi": "10.1007/s00044-026-03591-w",
  "fulltext_url": "https://europepmc.org/articles/PMC13669135",
  "id": "1ah2f4xtjne37",
  "issns": [
    "1054-2523",
    "1554-8120"
  ],
  "landing_url": "https://europepmc.org/article/MED/42873229",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1314|Adenosine and Purinergic Signaling"
    ]
  ],
  "openalex": "W7168037365",
  "pdf_url": "https://europepmc.org/articles/PMC13669135?pdf=render",
  "pmcid": "PMC13669135",
  "pmid": "42873229",
  "published": "2026-07-11",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/1ah2f4xtjne37.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:18Z",
      "native_id": "MED:42873229",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42873229"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:1314|Adenosine and Purinergic Signaling",
      "subfield": "physiology"
    }
  ],
  "title": "Investigation of reported small molecule P2Y6 receptor antagonists.",
  "title_text": "Investigation of reported small molecule P2Y6 receptor antagonists.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:18Z",
  "url": "https://research.draconitic.com/paper/1ah2f4xtjne37",
  "venue": "Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents",
  "versions": []
}