MK-7622: A First-in-Class M1 Positive Allosteric Modulator Development Candidate

  • ACS Med Chem Lett. 2018 Apr 30;9(7):652-656. doi: 10.1021/acsmedchemlett.8b00095.
Douglas C Beshore  1 ,  Christina N Di Marco  1 ,  Ronald K Chang  1 ,  Thomas J Greshock  1 ,  Lei Ma  1 ,  Marion Wittmann  1 ,  Matthew A Seager  1 ,  Kenneth A Koeplinger  1 ,  Charles D Thompson  1 ,  Joy Fuerst  1 ,  George D Hartman  1 ,  Mark T Bilodeau  1 ,  William J Ray  1 ,  Scott D Kuduk  1
Affiliations
  • 1. MRL, Merck & Co., Inc., Kenilworth, New Jersey 07033, United States.
PMID: 30034595 DOI: 10.1021/acsmedchemlett.8b00095
Abstract

Identification of ligands that selectively activate the M1 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 M1 muscarinic receptor that has entered Phase II studies in patients with Alzheimer's disease.

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