Evidence map›Paper›PMID 42460925›Full record

ArticleACS chemical neuroscience2026

Discovery of VU6081679, a Novel Positive Allosteric Modulator of Metabotropic Glutamate Receptor 8 with Efficacy in a Preclinical Model of Parkinson's Disease.

Alexa E Richardson, Anthony S Ferranti, Li Peng, Xia Lei, Allie Han, Aidong Qi, Alice L Rodriguez, Sichen Chang, Snehal Sant, Irene Zagol-Ikapitte and 17 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ACS chemical neuroscience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

27 authors.

Alexa E RichardsonWarren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee37232, United States.
Anthony S FerrantiWarren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee37232, United States.
Li PengWarren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee37232, United States.
Xia LeiWarren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee37232, United States.ORCID 0000-0003-3195-7190
Allie HanWarren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee37232, United States.
Aidong QiWarren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee37232, United States.
Alice L RodriguezWarren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee37232, United States.ORCID 0000-0002-5244-5103
Sichen ChangWarren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee37232, United States.
Snehal SantWarren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee37232, United States.
Irene Zagol-IkapitteWarren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee37232, United States.
Srinivasan KrishnanWarren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee37232, United States.
Analisa Thompson GrayWarren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee37232, United States.
Joshua C WilkinsonWarren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee37232, United States.
Sri H KethanapalliWarren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee37232, United States.
Hyekyung P ChoWarren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee37232, United States.
Kayla J TempleWarren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee37232, United States.ORCID 0000-0001-5290-574X
Dehui MiVanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee37232, United States.
Emily L DaysVanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee37232, United States.
Joshua A BauerVanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee37232, United States.
N Kithmini WijesiriDepartment of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee37232, United States.ORCID 0000-0003-4581-0448
Benjamin P BrownDepartment of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee37232, United States.
Olivier BoutaudWarren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee37232, United States.
Carrie K JonesWarren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee37232, United States.
Darren W EngersWarren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee37232, United States.
Craig W LindsleyWarren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee37232, United States.ORCID 0000-0003-0168-1445
Colleen M NiswenderWarren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee37232, United States.ORCID 0000-0001-6009-8212
Katherine E CrockerWarren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee37232, United States.ORCID 0009-0000-8835-4222

Funding

TRAINING IN PHARMACOLOGICAL SCIENCEST32GM007628 · NIGMS · VANDERBILT UNIVERSITY · PI BARNETT, JOEY VICTOR, KAVALALI, EGE T · 1985 to 2022
$11.2M
Development of mGlu7 receptor allosteric modulators for neurological and psychiatric disordersR01MH124671 · NIMH · VANDERBILT UNIVERSITY · PI LINDSLEY, CRAIG, NISWENDER, COLLEEN M · 2020 to 2024
$3.5M
Developing a computational platform for induced-fit and chemogenetic drug designDP1DA058349 · NIDA · VANDERBILT UNIVERSITY · PI Benjamin Patrick Brown · 2023 to 2026
$1.9M
JDRF JDRFI_2-SRA-2024-1460-M-BNational Institutes of Health (NIH) DP1DA058349National Institutes of Health (NIH) MH124671National Institutes of Health (NIH) T32 GM007628NIDA NIH HHS DP1 DA058349NIGMS NIH HHS T32 GM007628NIMH NIH HHS R01 MH124671Vanderbilt University NA
6 · The paper itself

Abstract

Herein, we report a potent, CNS penetrant, orally bioavailable metabotropic glutamate receptor subtype 8 (mGlu8) positive allosteric modulator (PAM), VU6081679, that shows robust efficacy in a rodent model of Parkinson's disease. A high-throughput screening effort and subsequent structure-activity relationship study led to the discovery of VU6081679, an mGlu8-preferring PAM with good potency at rat, mouse, and human mGlu8. Molecular docking into a published cryo-EM structure supports binding in an allosteric pocket at the extracellular TM6/TM7 dimer interface. VU6081679 displays a favorable rodent DMPK profile and demonstrates robust efficacy in a haloperidol-induced catalepsy model of Parkinson's disease in both rats and mice. Additional studies conducted in mGlu8 knockout mice confirmed that the observed efficacy is mGlu8-mediated.

Indexed as

Antiparkinson AgentsParkinson DiseaseReceptors, Metabotropic GlutamateAllosteric RegulationAnimalsCatalepsyDisease Models, AnimalHaloperidolHumansMaleMiceMice, KnockoutMolecular Docking SimulationRatsRats, Sprague-DawleyStructure-Activity RelationshipAntiparkinson AgentsHaloperidolmetabotropic glutamate receptor 8Receptors, Metabotropic Glutamatehaloperidol-induced catalepsyMetabotropic Glutamate Receptor Subtype 8mGlu8Parkinson’s diseasepositive allosteric modulator (PAM)VU6081679

Identifiers

PMID42460925
PMCPMC13449765

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.