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July 29, 2026Journal of Medicinal Chemistry

The Design, Synthesis and Pharmacological Characterization of Potent Xanomeline-Based M 1 and M 4 mAChR Bitopic Ligands

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Authors

YSYa SuVPVi PhamMKMichaela G. Kaoullas

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Overview

Experimental evaluation reveals improved selectivity and bias in novel bitopic ligands for targeted receptor subtypes.

Key Points

  • This research aims to design and synthesize effective bitopic ligands for muscarinic receptors M1 and M4.
  • Developed various bitopic ligands with different aliphatic linkers.
  • Evaluated signaling bias and selectivity across muscarinic receptor subtypes.
  • Identified best-performing compounds featuring diglycyl polyamide linkers.
  • Polymethylene-linked compounds showed minimal signaling bias and poor subtype selectivity.
  • PEG and polyamide linkers improved both signaling bias and selectivity.
  • Diglycyl polyamide linkers exhibited the highest subtype preference with pronounced signaling bias.

Cite This Study

Su et al. (2026) studied this question.

synapsesocial.com/papers/6a69a2e2c8da07d9defa6ebfhttps://doi.org/10.1021/acs.jmedchem.6c00895
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