{
  "abstract": "Background/Objectives: G protein-coupled receptors are a productive drug target family, yet clinical performance varies widely across rare, immune-mediated, pain, and thromboinflammatory diseases. We aimed to construct an explicit, stage-gated framework that makes translational prioritisation auditable and to examine whether it distinguishes clinically successful from unsuccessful programmes. Methods: This narrative, clinically anchored review included programmes with a stated human-disease rationale, Phase 2 or later clinical experience or a regulatory decision, and publicly accessible primary or regulatory documentation; evidence was considered through 7 August 2026. The cases spanned rare disease, immune-mediated inflammation, pain, and thromboinflammation. Thirteen programmes were reviewed, and eleven were entered into a retrospective five-axis scorecard covering human-disease anchoring, receptor pharmacology, modality and pharmacokinetic/pharmacodynamic feasibility, biomarker-to-endpoint readiness, and durability. Each axis was scored 0–2, weighted to 100 points, and subject to predefined hard-stop rules. Results: Established successes scored 80–100 points, whereas failed programmes scored 30–48. PAR4 scored 57.5 and therefore fell in the stop-and-rework band; avacopan scored 80 before approval but now triggers an Axis 5 hard stop. Equal weighting preserved the classifications of established successes and hard-stop failures but shifted PAR4 to 60.0, demonstrating sensitivity of a borderline programme to the weighting scheme. The scorecard localized failures mainly to redundancy, biomarker–endpoint disconnect, or durability/evidence-integrity gates. Conclusions: The framework is an explicit prioritisation aid, not an externally validated predictive model. Its main value is to identify missing evidence and non-compensable weaknesses; prospective independent validation, including inter-rater reliability testing, is required before portfolio use.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Physiology, College of Medicine, Dongguk University, Gyeongju 38066, Republic of Korea"
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yohan Seo"
    },
    {
      "affs": [
        0
      ],
      "name": "Joohan Woo"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1zdbd029vf7wh.bib",
  "cited_by": 0,
  "doi": "10.3390/ph19101510",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13708073/?tool=EBI",
  "id": "1zdbd029vf7wh",
  "issns": [
    "1424-8247"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13708073",
  "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": [
    [
      "lcc",
      "R"
    ],
    [
      "lcc",
      "RS1-441"
    ],
    [
      "openalex",
      "1312|Receptor Mechanisms and Signaling"
    ]
  ],
  "openalex": "W7214126620",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13708073/pdf/?tool=EBI",
  "pmcid": "PMC13708073",
  "pmid": null,
  "published": "2026-09-01",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/1zdbd029vf7wh.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:51Z",
      "native_id": "PMC:PMC13708073",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13708073"
    },
    {
      "first_seen": "2026-10-31T14:21:34Z",
      "native_id": "074ca9e15a8d41fd955aa20e7b3dae7d",
      "source": "doaj",
      "url": "https://doi.org/10.3390/ph19101510"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Receptor Mechanisms and Signaling",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Clinically Anchored GPCR Drug Discovery: Translational Lessons from Success, Failure, and Post-Approval Reassessment",
  "title_text": "Clinically Anchored GPCR Drug Discovery: Translational Lessons from Success, Failure, and Post-Approval Reassessment",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T14:21:34Z",
  "url": "https://research.draconitic.com/paper/1zdbd029vf7wh",
  "venue": "Pharmaceuticals (Basel, Switzerland)",
  "versions": []
}