Discovery of VU6077564: A Selective M₁ Antagonist That Promotes Neurite Outgrowth in Adult Sensory Neurons.

Authors

Tomayo I Berida, Cayden J Dodd, Joshua C Wilkinson, Darrell R Smith, Sichen Chang, Christopher C Presley, Li Peng, Snehal Sant, Srinivasan Krishnan, Irene Zagol-Ikapitte, Katherine J Watson, Analisa Thompson Gray, Alice L Rodriguez, Hyekyung P Cho, Carrie K Jones, Olivier Boutaud, Colleen M Niswender, Darren W Engers, Paul Fernyhough, Craig W Lindsley, Elizabeth S Childress

Published in

ACS chemical neuroscience. Jul 07, 2026. Epub Jul 07, 2026.

Abstract

Previously, we reported the potent and highly selective M₁ antagonists VU0415248 and VU0452865; however, these compounds were limited by high predicted hepatic clearance in rat. This work reports the development of cyclobutylsulfonamide-based analogs of VU0415248 and VU0452865. From this exercise, we identified VU6077564, a peripherally restricted and selective M₁ antagonist. Furthermore, we demonstrate the ability of VU6077564 to promote neurite outgrowth in adult rat dorsal root ganglia sensory neurons, highlighting the potential of selective M₁ antagonists for the treatment of peripheral neuropathy.

PMID:
42411178
Bibliographic data and abstract were imported from PubMed on 07 Jul 2026.

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