Fine Tuning Muscarinic Acetylcholine Receptor Signaling Through Allostery and Bias.

ABSTRACT: The M₁ and M₄ muscarinic acetylcholine receptors (mAChRs) are highly pursued drug targets for neurological diseases, in particular for Alzheimer's disease and schizophrenia. Due to high sequence homology, selective targeting of any of the M₁-M₅ mAChRs through the endogenous ligand binding site has been notoriously difficult to achieve. With the discovery of highly subtype selective mAChR positive allosteric modulators in the new millennium, selectivity through targeting an allosteric binding site has opened new avenues for drug discovery programs. However, some hurdles remain to be overcome for these promising new drug candidates to progress into the clinic. One challenge is the potential for on-target side effects, such as for the M₁

SUBMITTER: van der Westhuizen ET 

PROVIDER: S-EPMC7878563 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature