Mk-7622: A First-In-Class M-1 Positive Allosteric Modulator Development Candidate

Identification of ligands that selectively activate the M-1 muscarinic signaling pathway has been sought for decades to treat a range of neurological and cognitive disorders. Herein, we describe the optimization efforts focused on addressing key physicochemical and safety properties, ultimately leading to the clinical candidate MK-7622, a highly selective positive allosteric modulator of the M-1 muscarinic receptor that has entered Phase II studies in patients with Alzheimer's disease.