---
title: "BRD3290: Discovery of a GluA3‑Preferring AMPA Receptor Positive Allosteric Modulator"
id: "biorxiv-9-discovery-of-glua3-preferring-ampa-receptor-positive-allosteric-modulator"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-9-discovery-of-glua3-preferring-ampa-receptor-positive-allosteric-modulator"
content_type: "clinical_feed_article"
specialty: "Pharmacology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.07.26.740780v1?rss=1"
published_at: "2026-07-29T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# BRD3290: Discovery of a GluA3‑Preferring AMPA Receptor Positive Allosteric Modulator
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-9-discovery-of-glua3-preferring-ampa-receptor-positive-allosteric-modulator
- **Specialty:** [Pharmacology](https://medichelpline.com/clinical-feed/pharmacology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.07.26.740780v1?rss=1)
- **Published At:** 2026-07-29T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- The preprint reports the discovery of **BRD3290**, described as a **GluA3‑preferring AMPA receptor positive allosteric modulator** (PAM). - The work is presented as a research preprint on bioRxiv (doi: 10.64898/2026.07.26.740780) and has not been peer reviewed. - The author list includes multiple contributors affiliated with the Broad Institute of MIT and Harvard; correspondence is directed to Sean P Moran (smoran@broadinstitute.org). - The title and abstract indicate a connection to neuropsychiatric disease; the abstract begins by naming **schizophrenia** as a clinical context but the provided excerpt is truncated and does not include study details. - Supplementary material and a full PDF are available via the bioRxiv entry, but the supplied source excerpt does not include methods, experimental data, pharmacological characterization, selectivity metrics, or in vivo findings. - Key experimental results, potency, selectivity data for **GluA3** vs other AMPA subunits, structural or medicinal chemistry details, and any proposed therapeutic implications are not reported in the excerpt supplied. - Readers should consult the full preprint and supplementary materials on bioRxiv for complete experimental methods, data, and authors' conclusions; until peer review, findings should be regarded as preliminary.
## Clinical Analysis & Structured Key Points
Discovery of GluA3 preferring AMPA receptor positive allosteric modulator BRD3290 | bioRxiv Skip to main content New Results Discovery of GluA3 preferring AMPA receptor positive allosteric modulator BRD3290 Christopher Greaves , William E Martenis , View ORCID Profile Shawn D Nelson Jr. , Jon Madison , Adam Skepner , David Baez-Nieto , Katherine J Stalnaker , Evan P Lebois , Arthur J Campbell , Katie Pelham , Mihaela Magdei , Alex Guletsky , Karen Perez de Arce , Yan-Ling Zhang , Florence F Wagner , View ORCID Profile Jen Qian Pan , Michel Weïwer , Morgan Sheng , View ORCID Profile Sean P Moran doi: https://doi.org/10.64898/2026.07.26.740780 Christopher Greaves Broad Institute of MIT and Harvard Find this author on Google Scholar Find this author on PubMed Search for this author on this site William E Martenis Broad Institute of MIT and Harvard Find this author on Google Scholar Find this author on PubMed Search for this author on this site Shawn D Nelson Jr. Broad Institute of MIT and Harvard Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Shawn D Nelson Jr. Jon Madison Broad Institute of MIT and Harvard Find this author on Google Scholar Find this author on PubMed Search for this author on this site Adam Skepner Broad Institute of MIT and Harvard Find this author on Google Scholar Find this author on PubMed Search for this author on this site David Baez-Nieto Broad Institute of MIT and Harvard Find this author on Google Scholar Find this author on PubMed Search for this author on this site Katherine J Stalnaker Broad Institute of MIT and Harvard Find this author on Google Scholar Find this author on PubMed Search for this author on this site Evan P Lebois Broad Institute of MIT and Harvard Find this author on Google Scholar Find this author on PubMed Search for this author on this site Arthur J Campbell Broad Institute of MIT and Harvard Find this author on Google Scholar Find this author on PubMed Search for this author on this site Katie Pelham Broad Institute of MIT and Harvard Find this author on Google Scholar Find this author on PubMed Search for this author on this site Mihaela Magdei Broad Institute of MIT and Harvard Find this author on Google Scholar Find this author on PubMed Search for this author on this site Alex Guletsky Broad Institute of MIT and Harvard Find this author on Google Scholar Find this author on PubMed Search for this author on this site Karen Perez de Arce Broad Institute of MIT and Harvard Find this author on Google Scholar Find this author on PubMed Search for this author on this site Yan-Ling Zhang Broad Institute of MIT and Harvard Find this author on Google Scholar Find this author on PubMed Search for this author on this site Florence F Wagner Broad Institute of MIT and Harvard Find this author on Google Scholar Find this author on PubMed Search for this author on this site Jen Qian Pan Broad Institute of MIT and Harvard Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Jen Qian Pan Michel Weïwer Broad Institute of MIT and Harvard Find this author on Google Scholar Find this author on PubMed Search for this author on this site Morgan Sheng Broad Institute of MIT and Harvard Find this author on Google Scholar Find this author on PubMed Search for this author on this site Sean P Moran Broad Institute of MIT and Harvard Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Sean P Moran For correspondence: smoran{at}broadinstitute.org Abstract Info/History Metrics Supplementary material Preview PDF Abstract Schizophrenia is a debilitating neuropsychiatric disease that lacks effective treatments for many symptom domains including negative, cognitive and sleep disturbances. Lack of clear disease etiology has hampered the development of new, effective treatments for the unmet needs of people with schizophrenia. Large scale human genetics have identified rare loss of function mutations that substantially increase risk of developing schizophrenia, including in GRIA3, the gene that encodes the GluA3 receptor subunit of the AMPA receptor (AMPAR). Several drug discovery programs have been aimed at developing AMPAR positive allosteric modulators (PAMs) as a novel treatment for schizophrenia. Despite intense drug discovery efforts, there are no FDA approved AMPAR PAMs. We therefore hypothesized that selectively targeting GluA3, the AMPAR subunit implicated by human genetics, could yield a safer and more effective AMPAR PAM for the potential treatment of schizophrenia. Using a combination of medicinal chemistry, in vitro, and in vivo studies, we discovered BRD3290, a GluA3-preferring AMPAR PAM with reasonable potency in heterologous cells, as well as favorable tolerability and brain exposure. Peripheral administration of BRD3290 engaged an established AMPAR PAM target engagement biomarker but did not improve performance of wildtype mice in the novel object recognition task (NOR), in contrast to the nonselective AMPAR PAM PF-4778574, which improved mouse NOR. These findings suggest that the GluA3 selectivity profile of BRD3290 was insufficient to enhance cognitive function in this mouse NOR paradigm. This work highlights the challenges of AMPAR subtype-selective modulation and provides molecular insights into the ability to develop subtype-selective AMPAR PAMs. Competing Interest Statement The authors have declared no competing interest. Funder Information Declared Stanley Center for Psychiatric Research Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Back to top Previous Next Posted July 29, 2026. Download PDF Supplementary Material Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following Discovery of GluA3 preferring AMPA receptor positive allosteric modulator BRD3290 Message Subject (Your Name) has forwarded a page to you from bioRxiv Message Body (Your Name) thought you would like to see this page from the bioRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Share Discovery of GluA3 preferring AMPA receptor positive allosteric modulator BRD3290 Christopher Greaves , William E Martenis , Shawn D Nelson Jr. , Jon Madison , Adam Skepner , David Baez-Nieto , Katherine J Stalnaker , Evan P Lebois , Arthur J Campbell , Katie Pelham , Mihaela Magdei , Alex Guletsky , Karen Perez de Arce , Yan-Ling Zhang , Florence F Wagner , Jen Qian Pan , Michel Weïwer , Morgan Sheng , Sean P Moran bioRxiv 2026.07.26.740780; doi: https://doi.org/10.64898/2026.07.26.740780 Share This Article: Copy Citation Tools Discovery of GluA3 preferring AMPA receptor positive allosteric modulator BRD3290 Christopher Greaves , William E Martenis , Shawn D Nelson Jr. , Jon Madison , Adam Skepner , David Baez-Nieto , Katherine J Stalnaker , Evan P Lebois , Arthur J Campbell , Katie Pelham , Mihaela Magdei , Alex Guletsky , Karen Perez de Arce , Yan-Ling Zhang , Florence F Wagner , Jen Qian Pan , Michel Weïwer , Morgan Sheng , Sean P Moran bioRxiv 2026.07.26.740780; doi: https://doi.org/10.64898/2026.07.26.740780 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Areas All Articles Animal Behavior and Cognition (7835) Biochemistry (18320) Bioengineering (14499) Bioinformatics (43335) Biophysics (22077) Cancer Biology (19196) Cell Biology (26318) Clinical Trials (138) Developmental Biology (13707) Ecology (20518) Epidemiology (2067) Evolutionary Biology (24968) Genetics (15913) Genomics (23107) Immunology (18304) Microbiology (41552) Molecular Biology (17631) Neuroscience (91381) Paleontology (683) Pathology (2927) Pharmacology and Toxicology (4975) Physiology (7923) Plant Biology (15600) Scientific Communication and Education (2073) Synthetic Biology (4449) Systems Biology (10047) Zoology (2331)
## Related Clinical Research

- [International trends in clozapine utilisation prevalence in 42 countries, 2015–2024](https://medichelpline.com/clinical-feed/medrxiv-9-international-trends-in-clozapine-utilisation-prevalence-in-adults-adolescents.md)
- [Acetylcholine Receptor Agonists Reduce Ethanol Self-Administration in Cynomolgus Monkeys: Varenicl](https://medichelpline.com/clinical-feed/pubmed-42562046.md) (DOI: 10.1016/j.ejphar.2026.179199)
- [Understanding Parasitic Identification in Delusional Parasitosis](https://medichelpline.com/clinical-feed/plos-one-21-bridging-perception-and-reality-parasitic-identification-in-delusional.md)
- [Spatial novelty alters N100m but not the 40-Hz auditory steady-state response](https://medichelpline.com/clinical-feed/pubmed-42229828.md) (DOI: 10.1016/j.neuroscience.2026.05.042)
- [Adjunctive pharmacological and non‑pharmacological treatments for negative symptoms of schizophren](https://medichelpline.com/clinical-feed/medrxiv-16-comparative-efficacy-of-pharmacological-and-non-pharmacological-adjunctive.md)

## Navigation
- [← Back to Pharmacology Feed](https://medichelpline.com/clinical-feed/pharmacology.md)
- [← All Clinical Specialties](https://medichelpline.com/clinical-feed.md)
## Medical & Regulatory Disclaimer

> [!CAUTION]
> MedicHelpline content is structured for research, educational, and professional discovery purposes. It does not constitute individual medical advice, clinical diagnosis, or treatment recommendations.
> Always verify dosing, contraindications, and regulatory alerts against official product labeling and primary regulatory sources before clinical decision-making.