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June 6, 2026ACS Chemical NeuroscienceOpen Access

Discovery of VU6053371/BI03738809: A First-in-Class Selective and CNS-Penetrant mGlu ₃ Positive Allosteric Modulator (PAM) with Efficacy in a Preclinical Cognition Model

Caleb A. Jones Renn A. Duncan Kristen Gilliland Carson W. Reed Daniel H. Haymer Paul K. Spearing Rory A. Capstick Bartholomew P. Roland Paige Vinson Marc Quitalig Caroline Baggeroer Natasha B. Billard Jonathan W. Dickerson Zixiu Xiang Valerie M. Kramlinger Olivier Boutaud Julia Schlichtiger Carrie K. Jones Colleen M. Niswender Hyekyung P. Cho Jerri L. Rook Carsten T. Wotjak Matthias Freiwald Riccardo Giovannini Heiko Sommer Scott Hobson P. Jeffrey Conn Bruce J. Melancon Craig W. Lindsley

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Key Points

The aim is to discover a first-in-class mGlu3 positive allosteric modulator with CNS penetration and efficacy in cognition.
Developed and tested VU6053371 for its selectivity and CNS penetration.
Evaluated efficacy in a preclinical cognition model.
VU6053371 showed significant improvement in cognitive performance in the preclinical model.
Demonstrated selective modulation of mGlu3 without affecting other mGlu receptor subtypes.

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Implication

Preclinical trial demonstrates efficacy of a novel mGlu3 positive allosteric modulator in cognition.

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Cite This Study

Jones et al. (2026) studied this question.

synapsesocial.com/papers/6a265ccbad53cfb9357c609c https://doi.org/10.1021/acschemneuro.6c00325

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