Development of covalent agonists for the muscarinic acetylcholine receptor

Eitel K, Risel P, Kaindl J, Einsiedel J, Hübner H, Gmeiner P (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Book Volume: 143

Article Number: 118783

DOI: 10.1016/j.bmc.2026.118783

Abstract

Binding affinity and residence time of endogenous and synthetic receptor ligands are often poor at the tissue to be treated. Covalent ligands targeting G protein-coupled receptors (GPCRs) have gained significant interest because they unite the high specificity and selectivity with the prolonged activity resulting from irreversible or slowly reversible binding. Using the muscarinic acetylcholine receptor (mAChR) agonists iperoxo (5), PR15 (7), and carbachol (9) as lead compounds, we developed the covalent muscarinic receptor agonists 8 and 10 functionalized by a mustard-type reactive group. Radioligand depletion and functional properties clearly indicated covalent binding and activation of the therapeutically relevant muscarinic acetylcholine receptor.

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How to cite

APA:

Eitel, K., Risel, P., Kaindl, J., Einsiedel, J., Hübner, H., & Gmeiner, P. (2026). Development of covalent agonists for the muscarinic acetylcholine receptor. Bioorganic & Medicinal Chemistry, 143. https://doi.org/10.1016/j.bmc.2026.118783

MLA:

Eitel, Katrin, et al. "Development of covalent agonists for the muscarinic acetylcholine receptor." Bioorganic & Medicinal Chemistry 143 (2026).

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