{
  "abstract": "In this study, we employed an extensive drug repurposing strategy to identify new and improved adenosine receptor (AR) antagonists, with the aim of uncovering alternative therapeutic applications for existing polycyclic drug-like molecules. The compounds selected from our library were initially tested using the NanoBRET assay, and the top hits were then subjected to a predictive molecular modeling study, which enabled us to guide the design of new adenosine A1 and A3 receptor (A1R/A3R) antagonists. This approach led to the identification of two lead candidates, which exhibit a different profile of affinity and selectivity toward the A1R and A3R subtypes, attributable to their specific structural features. In particular, compound 2v (based on a pyrazolo[1,5-a]pyrimidine scaffold) showed the highest affinity, with a 10-fold greater selectivity toward A1R (pKi of 8.18 ± 0.21 and 6.76 ± 0.11 on A1R and A3R, respectively). These results highlight the critical role of the substituted phenyl group at position 2 in conferring A1R selectivity. In contrast, compound 3f (based on a tricyclic scaffold) proved to be a potent and selective A3R antagonist (pKi = 6.94 for A1R and 8.22 for A3R). Collectively, these findings provide valuable insights for the development of improved small-molecule heterocyclic A1R/A3R antagonists and may support future therapeutic applications targeting these receptor subtypes.",
  "abstract_shown": true,
  "affiliations": [
    "University of Cambridge , , Tennis Court Road , ,",
    "University of Florence , , Via Ugo Schiff 6 , ,",
    "King’s College London , , Stamford Street , ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Abigail Pearce",
      "orcid": "0000-0001-9845-0541"
    },
    {
      "affs": [
        1
      ],
      "name": "Letizia Crocetti",
      "orcid": "0000-0003-3473-2683"
    },
    {
      "affs": [
        2
      ],
      "name": "Qi Xu"
    },
    {
      "affs": [
        1
      ],
      "name": "Francesca Catarzi"
    },
    {
      "affs": [
        1
      ],
      "name": "Gabriella Guerrini",
      "orcid": "0000-0001-6711-7965"
    },
    {
      "affs": [
        2
      ],
      "name": "Zihan Shi"
    },
    {
      "affs": [
        0
      ],
      "name": "Ana Rossi"
    },
    {
      "affs": [
        0
      ],
      "name": "Alex Harper"
    },
    {
      "affs": [
        0
      ],
      "name": "Ayoola Ishola"
    },
    {
      "affs": [
        0
      ],
      "name": "Shahd Abdelrahman"
    },
    {
      "affs": [
        0
      ],
      "name": "Yashkumar Patel",
      "orcid": "0009-0009-5424-0767"
    },
    {
      "affs": [
        0
      ],
      "name": "Xianglin Huang"
    },
    {
      "affs": [
        1
      ],
      "name": "Silvia Selleri"
    },
    {
      "affs": [
        1
      ],
      "name": "Maria Paola Giovannoni",
      "orcid": "0000-0003-0310-7850"
    },
    {
      "affs": [
        2
      ],
      "name": "Agostino Cilibrizzi",
      "orcid": "0000-0002-9711-5183"
    },
    {
      "affs": [
        0
      ],
      "name": "Graham Ladds",
      "orcid": "0000-0001-7320-9612"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4d76phqbt3s02.bib",
  "cited_by": 0,
  "doi": "10.1021/acsomega.6c07719",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13717783/?tool=EBI",
  "id": "4d76phqbt3s02",
  "issns": [
    "2470-1343"
  ],
  "landing_url": "https://pubs.acs.org/acsodf/article/11/42/65290/5448928/Repurposing-Based-Strategies-to-Identify-Effective",
  "language": "eng",
  "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": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "1314|Adenosine and Purinergic Signaling"
    ]
  ],
  "openalex": "W7221527658",
  "pdf_url": "https://pubs.acs.org/doi/pdf/10.1021/acsomega.6c07719",
  "pmcid": "PMC13717783",
  "pmid": "42959995",
  "published": "2026-10-12",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/4d76phqbt3s02.ris",
  "sources": [
    {
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      "native_id": "10.1021/acsomega.6c07719",
      "source": "crossref",
      "url": "https://pubs.acs.org/acsodf/article/11/42/65290/5448928/Repurposing-Based-Strategies-to-Identify-Effective"
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    {
      "first_seen": "2026-10-31T00:20:37Z",
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      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13717783"
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      "url": "https://europepmc.org/article/MED/42959995"
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    {
      "first_seen": "2026-11-02T12:22:02Z",
      "native_id": "PMC13717783",
      "source": "pmc",
      "url": "https://doi.org/10.1021/acsomega.6c07719"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:1314|Adenosine and Purinergic Signaling",
      "subfield": "physiology"
    }
  ],
  "title": "Repurposing-Based Strategies to Identify Effective Adenosine Receptor Antagonists",
  "title_text": "Repurposing-Based Strategies to Identify Effective Adenosine Receptor Antagonists",
  "type": "peer-reviewed",
  "updated_at": "2026-11-02T12:22:02Z",
  "url": "https://research.draconitic.com/paper/4d76phqbt3s02",
  "venue": "ACS Omega",
  "versions": []
}