{
  "abstract": "The metabotropic glutamate receptor 7 (mGlu7) is an emerging therapeutic target for central nervous system disorders, but progress has been limited by a lack of selective pharmacological tools. CVN636 was recently reported as a potent and selective allosteric agonist of this receptor, capable of receptor activation in the absence of glutamate, with demonstrated efficacy in a rodent model of alcohol use disorder. Here, using complementary bioluminescence resonance energy transfer-based assays that measure both downstream signaling and G protein recruitment, we show that CVN636 does not activate the receptor on its own. Instead, CVN636 acts as a positive allosteric modulator that enhances the potency and efficacy of orthosteric agonist responses, including those of glutamate, in an agonist-dependent manner. Blockade of orthosteric agonist binding with a competitive antagonist abolished CVN636 activity, consistent with this mechanism. Furthermore, using an assay that distinguishes signaling from defined receptor dimers, we find that CVN636 activity is selective for mGlu7/7 homodimers and does not extend to any mGlu7-containing heterodimer tested. Thus, in our assay system CVN636 is an mGlu7/7 homodimer-selective positive allosteric modulator of this receptor, suggesting that its in vivo actions likely stem from action at these homomers.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Psychiatry, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "name": "X. Lin"
    },
    {
      "name": "C. M. Niswender"
    },
    {
      "name": "W. B. Asher"
    },
    {
      "affs": [
        0
      ],
      "name": "J. A. Javitch"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e1scw040dtm81.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.17.759826",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.17.759826v1.full",
  "id": "e1scw040dtm81",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.17.759826v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "pharmacology and toxicology"
    ],
    [
      "openalex",
      "1312|Receptor Mechanisms and Signaling"
    ]
  ],
  "openalex": "W7222914175",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.17.759826v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-17",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/e1scw040dtm81.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:28:29Z",
      "native_id": "10.64898/2026.10.17.759826",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.17.759826v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:pharmacology and toxicology",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "CVN636 potentiates orthosteric agonist responses selectively at mGlu7/7 homodimers",
  "title_text": "CVN636 potentiates orthosteric agonist responses selectively at mGlu7/7 homodimers",
  "type": "preprint",
  "updated_at": "2026-10-30T12:28:29Z",
  "url": "https://research.draconitic.com/paper/e1scw040dtm81",
  "venue": "bioRxiv",
  "versions": []
}