Literature DB >> 30034595

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

Douglas C Beshore1, Christina N Di Marco1, Ronald K Chang1, Thomas J Greshock1, Lei Ma1, Marion Wittmann1, Matthew A Seager1, Kenneth A Koeplinger1, Charles D Thompson1, Joy Fuerst1, George D Hartman1, Mark T Bilodeau1, William J Ray1, Scott D Kuduk1.   

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.

Entities:  

Year:  2018        PMID： 30034595      PMCID： PMC6047034          DOI： 10.1021/acsmedchemlett.8b00095

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  23 in total

Review 1.  The molecular basis of muscarinic receptor diversity.

Authors:  T I Bonner
Journal:  Trends Neurosci       Date:  1989-04       Impact factor: 13.837

2.  Effects of xanomeline, a selective muscarinic receptor agonist, on cognitive function and behavioral symptoms in Alzheimer disease.

Authors:  N C Bodick; W W Offen; A I Levey; N R Cutler; S G Gauthier; A Satlin; H E Shannon; G D Tollefson; K Rasmussen; F P Bymaster; D J Hurley; W Z Potter; S M Paul
Journal:  Arch Neurol       Date:  1997-04

Review 3.  New subtypes of muscarinic acetylcholine receptors.

Authors:  T I Bonner
Journal:  Trends Pharmacol Sci       Date:  1989-12       Impact factor: 14.819

4.  Quinolizidinone carboxylic acids as CNS penetrant, selective m1 allosteric muscarinic receptor modulators.

Authors:  Scott D Kuduk; Ronald K Chang; Christina N Di Marco; William J Ray; Lei Ma; Marion Wittmann; Matthew A Seager; Kenneth A Koeplinger; Charles D Thompson; George D Hartman; Mark T Bilodeau
Journal:  ACS Med Chem Lett       Date:  2010-06-04       Impact factor: 4.345

Review 5.  Muscarinic agonists and antagonists in the treatment of Alzheimer's disease.

Authors:  W Greenlee; J Clader; T Asberom; S McCombie; J Ford; H Guzik; J Kozlowski; S Li; C Liu; D Lowe; S Vice; H Zhao; G Zhou; W Billard; H Binch; R Crosby; R Duffy; J Lachowicz; V Coffin; R Watkins; V Ruperto; C Strader; L Taylor; K Cox
Journal:  Farmaco       Date:  2001-04

6.  Selective activation of the M1 muscarinic acetylcholine receptor achieved by allosteric potentiation.

Authors:  Lei Ma; Matthew A Seager; Matthew Seager; Marion Wittmann; Marlene Jacobson; Denise Bickel; Maryann Burno; Keith Jones; Valerie Kuzmick Graufelds; Guangping Xu; Michelle Pearson; Alexander McCampbell; Renee Gaspar; Paul Shughrue; Andrew Danziger; Christopher Regan; Rose Flick; Danette Pascarella; Susan Garson; Scott Doran; Constantine Kreatsoulas; Lone Veng; Craig W Lindsley; William Shipe; Scott Kuduk; Cyrille Sur; Gene Kinney; Guy R Seabrook; William J Ray
Journal:  Proc Natl Acad Sci U S A       Date:  2009-08-26       Impact factor: 11.205

Review 7.  SAR studies on carboxylic acid series M(1) selective positive allosteric modulators (PAMs).

Authors:  Scott D Kuduk; Douglas C Beshore
Journal:  Curr Top Med Chem       Date:  2014       Impact factor: 3.295

Review 8.  Allosteric modulators of GPCRs: a novel approach for the treatment of CNS disorders.

Authors:  P Jeffrey Conn; Arthur Christopoulos; Craig W Lindsley
Journal:  Nat Rev Drug Discov       Date:  2009-01       Impact factor: 84.694

Review 9.  Muscarinic acetylcholine receptors as CNS drug targets.

Authors:  Christopher J Langmead; Jeannette Watson; Charlie Reavill
Journal:  Pharmacol Ther       Date:  2007-12-20       Impact factor: 12.310

10.  Knowledge-Based, Central Nervous System (CNS) Lead Selection and Lead Optimization for CNS Drug Discovery.

Authors:  Arup K Ghose; Torsten Herbertz; Robert L Hudkins; Bruce D Dorsey; John P Mallamo
Journal:  ACS Chem Neurosci       Date:  2011-11-02       Impact factor: 4.418
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  8 in total

Review 1.  Drug Design Targeting the Muscarinic Receptors and the Implications in Central Nervous System Disorders.

Authors:  Chad R Johnson; Brian D Kangas; Emily M Jutkiewicz; Jack Bergman; Andrew Coop
Journal:  Biomedicines       Date:  2022-02-07

Review 2.  Selective Modulation of Dynamic Protein Complexes.

Authors:  Julie M Garlick; Anna K Mapp
Journal:  Cell Chem Biol       Date:  2020-08-11       Impact factor: 8.116

3.  Cryptic pocket formation underlies allosteric modulator selectivity at muscarinic GPCRs.

Authors:  Scott A Hollingsworth; Brendan Kelly; Celine Valant; Jordan Arthur Michaelis; Olivia Mastromihalis; Geoff Thompson; A J Venkatakrishnan; Samuel Hertig; Peter J Scammells; Patrick M Sexton; Christian C Felder; Arthur Christopoulos; Ron O Dror
Journal:  Nat Commun       Date:  2019-07-23       Impact factor: 14.919

4.  T-495, a novel low cooperative M1 receptor positive allosteric modulator, improves memory deficits associated with cholinergic dysfunction and is characterized by low gastrointestinal side effect risk.

Authors:  Takao Mandai; Yuu Sako; Emi Kurimoto; Yuji Shimizu; Minoru Nakamura; Makoto Fushimi; Ryouta Maeda; Maki Miyamoto; Haruhide Kimura
Journal:  Pharmacol Res Perspect       Date:  2020-02

Review 5.  Fine Tuning Muscarinic Acetylcholine Receptor Signaling Through Allostery and Bias.

Authors:  Emma T van der Westhuizen; K H Christopher Choy; Celine Valant; Simon McKenzie-Nickson; Sophie J Bradley; Andrew B Tobin; Patrick M Sexton; Arthur Christopoulos
Journal:  Front Pharmacol       Date:  2021-01-29       Impact factor: 5.810

Review 6.  Multitargeting nature of muscarinic orthosteric agonists and antagonists.

Authors:  Jaromir Myslivecek
Journal:  Front Physiol       Date:  2022-09-06       Impact factor: 4.755

7.  Discovery of a novel class of heteroaryl-pyrrolidinones as positive allosteric modulators of the muscarinic acetylcholine receptor M1.

Authors:  Paul K Spearing; Hyekyung P Cho; Vincent B Luscombe; Anna L Blobaum; Olivier Boutaud; Darren W Engers; Alice L Rodriguez; Colleen M Niswender; P Jeffrey Conn; Craig W Lindsley; Aaron M Bender
Journal:  Bioorg Med Chem Lett       Date:  2021-06-09       Impact factor: 2.940

8.  Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes-3.

Authors:  Arduino A Mangoni; Tiziano Tuccinardi; Simona Collina; Jean Jacques Vanden Eynde; Diego Muñoz-Torrero; Rafik Karaman; Carlo Siciliano; Maria Emília de Sousa; Katalin Prokai-Tatrai; Jarkko Rautio; Catherine Guillou; Michael Gütschow; Stefania Galdiero; Hong Liu; Luigi A Agrofoglio; Jean-Marc Sabatier; Christopher Hulme; George Kokotos; Qidong You; Paula A C Gomes
Journal:  Molecules       Date:  2018-06-30       Impact factor: 4.411
  8 in total

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