Journal
ACS MEDICINAL CHEMISTRY LETTERS
Volume 9, Issue 7, Pages 652-656Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsmedchemlett.8b00095
Keywords
M-1; muscarinic; positive allosteric modulator; M-1 PAM; MK-7622
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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.
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