A Novel Multivalent Ligand That Bridges the Allosteric and Orthosteric Binding Sites of the M2 Muscarinic Receptor

@article{Steinfeld2007ANM,
  title={A Novel Multivalent Ligand That Bridges the Allosteric and Orthosteric Binding Sites of the M2 Muscarinic Receptor},
  author={Tod Steinfeld and Mathai Mammen and Jacqueline A. M. Smith and Richard D Wilson and Jeffrey R. Jasper},
  journal={Molecular Pharmacology},
  year={2007},
  volume={72},
  pages={291 - 302}
}
THRX-160209 is a potent antagonist at the M2 muscarinic acetylcholine (ACh) receptor subtype that was designed using a multivalent strategy, simultaneously targeting the orthosteric site and a nearby site known to bind allosteric ligands. In this report, we describe three characteristics of THRX-160209 binding that are consistent with a multivalent interaction: 1) an apparent affinity of the multivalent ligand for the M2 receptor subtype (apparent pKI = 9.51 ± 0.22) that was several orders of… 

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