Literature DB >> 23916258

Discovery and SAR of a novel series of GIRK1/2 and GIRK1/4 activators.

Susan J Ramos-Hunter1, Darren W Engers, Kristian Kaufmann, Yu Du, Craig W Lindsley, C David Weaver, Gary A Sulikowski.   

Abstract

This Letter describes a novel series of GIRK activators identified through an HTS campaign. The HTS lead was a potent and efficacious dual GIRK1/2 and GIRK1/4 activator. Further chemical optimization through both iterative parallel synthesis and fragment library efforts identified dual GIRK1/2 and GIRK1/4 activators as well as the first examples of selective GIRK1/4 activators. Importantly, these compounds were inactive on GIRK2 and other non-GIRK1 containing GIRK channels, and SAR proved shallow.
Copyright © 2013 Elsevier Ltd. All rights reserved.

Entities:  

Keywords:  Activators; GIRK; K(ir)3.x; Thallium flux

Mesh：

Substances：

Year:  2013        PMID： 23916258      PMCID： PMC4066871          DOI： 10.1016/j.bmcl.2013.07.002

Source DB:  PubMed          Journal:  Bioorg Med Chem Lett        ISSN： 0960-894X            Impact factor:   2.823


  12 in total

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2.  ML297 (VU0456810), the first potent and selective activator of the GIRK potassium channel, displays antiepileptic properties in mice.

Authors:  Kristian Kaufmann; Ian Romaine; Emily Days; Conrado Pascual; Adam Malik; Liya Yang; Bende Zou; Yu Du; Greg Sliwoski; Ryan D Morrison; Jerod Denton; Colleen M Niswender; J Scott Daniels; Gary A Sulikowski; Xinmin Simon Xie; Craig W Lindsley; C David Weaver
Journal:  ACS Chem Neurosci       Date:  2013-06-13       Impact factor: 4.418

Review 3.  Emerging roles for G protein-gated inwardly rectifying potassium (GIRK) channels in health and disease.

Authors:  Christian Lüscher; Paul A Slesinger
Journal:  Nat Rev Neurosci       Date:  2010-04-14       Impact factor: 34.870

4.  Ethanol opens G-protein-activated inwardly rectifying K+ channels.

Authors:  T Kobayashi; K Ikeda; H Kojima; H Niki; R Yano; T Yoshioka; T Kumanishi
Journal:  Nat Neurosci       Date:  1999-12       Impact factor: 24.884

5.  Molecular cloning of a mouse G-protein-activated K+ channel (mGIRK1) and distinct distributions of three GIRK (GIRK1, 2 and 3) mRNAs in mouse brain.

Authors:  T Kobayashi; K Ikeda; T Ichikawa; S Abe; S Togashi; T Kumanishi
Journal:  Biochem Biophys Res Commun       Date:  1995-03-28       Impact factor: 3.575

6.  Primary structure and functional expression of a rat G-protein-coupled muscarinic potassium channel.

Authors:  Y Kubo; E Reuveny; P A Slesinger; Y N Jan; L Y Jan
Journal:  Nature       Date:  1993-08-26       Impact factor: 49.962

7.  The G-protein-gated atrial K+ channel IKACh is a heteromultimer of two inwardly rectifying K(+)-channel proteins.

Authors:  G Krapivinsky; E A Gordon; K Wickman; B Velimirović; L Krapivinsky; D E Clapham
Journal:  Nature       Date:  1995-03-09       Impact factor: 49.962

8.  Discovery of positive allosteric modulators for the metabotropic glutamate receptor subtype 5 from a series of N-(1,3-diphenyl-1H- pyrazol-5-yl)benzamides that potentiate receptor function in vivo.

Authors:  Craig W Lindsley; David D Wisnoski; William H Leister; Julie A O'brien; Wei Lemaire; David L Williams; Maryann Burno; Cyrille Sur; Gene G Kinney; Doug J Pettibone; Philip R Tiller; Sheri Smith; Mark E Duggan; George D Hartman; P Jeffrey Conn; Joel R Huff
Journal:  J Med Chem       Date:  2004-11-18       Impact factor: 7.446

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Authors:  Prafulla Aryal; Hay Dvir; Senyon Choe; Paul A Slesinger
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10.  Cloning provides evidence for a family of inward rectifier and G-protein coupled K+ channels in the brain.

Authors:  F Lesage; F Duprat; M Fink; E Guillemare; T Coppola; M Lazdunski; J P Hugnot
Journal:  FEBS Lett       Date:  1994-10-10       Impact factor: 4.124
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  12 in total

Review 1.  Behavioral and Genetic Evidence for GIRK Channels in the CNS: Role in Physiology, Pathophysiology, and Drug Addiction.

Authors:  Jody Mayfield; Yuri A Blednov; R Adron Harris
Journal:  Int Rev Neurobiol       Date:  2015-06-22       Impact factor: 3.230

2.  VU0810464, a non-urea G protein-gated inwardly rectifying K+ (Kir 3/GIRK) channel activator, exhibits enhanced selectivity for neuronal Kir 3 channels and reduces stress-induced hyperthermia in mice.

Authors:  Baovi N Vo; Kristopher K Abney; Allison Anderson; Ezequiel Marron Fernandez de Velasco; Michael A Benneyworth; John Scott Daniels; Ryan D Morrison; Corey R Hopkins; Charles David Weaver; Kevin Wickman
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3.  Discovery, synthesis and characterization of a series of (1-alkyl-3-methyl-1H-pyrazol-5-yl)-2-(5-aryl-2H-tetrazol-2-yl)acetamides as novel GIRK1/2 potassium channel activators.

Authors:  Swagat Sharma; Krystian A Kozek; Kristopher K Abney; Sushil Kumar; Nagsen Gautam; Yazen Alnouti; C David Weaver; Corey R Hopkins
Journal:  Bioorg Med Chem Lett       Date:  2019-01-23       Impact factor: 2.823

4.  Discovery and Characterization of 1H-Pyrazol-5-yl-2-phenylacetamides as Novel, Non-Urea-Containing GIRK1/2 Potassium Channel Activators.

Authors:  Joshua M Wieting; Anish K Vadukoot; Swagat Sharma; Kristopher K Abney; Thomas M Bridges; J Scott Daniels; Ryan D Morrison; Kevin Wickman; C David Weaver; Corey R Hopkins
Journal:  ACS Chem Neurosci       Date:  2017-07-19       Impact factor: 4.418

5.  Analgesic Effects of the GIRK Activator, VU0466551, Alone and in Combination with Morphine in Acute and Persistent Pain Models.

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Journal:  ACS Chem Neurosci       Date:  2018-12-11       Impact factor: 4.418

6.  Discovery, synthesis and biological characterization of a series of N-(1-(1,1-dioxidotetrahydrothiophen-3-yl)-3-methyl-1H-pyrazol-5-yl)acetamide ethers as novel GIRK1/2 potassium channel activators.

Authors:  Swagat Sharma; Lauren Lesiak; Christopher D Aretz; Yu Du; Sushil Kumar; Nagsen Gautam; Yazen Alnouti; Nikilesh V Dhuria; Yashpal S Chhonker; C David Weaver; Corey R Hopkins
Journal:  RSC Med Chem       Date:  2021-06-21

Review 7.  New insights into the therapeutic potential of Girk channels.

Authors:  Rafael Luján; Ezequiel Marron Fernandez de Velasco; Carolina Aguado; Kevin Wickman
Journal:  Trends Neurosci       Date:  2013-11-21       Impact factor: 13.837

Review 8.  Advances in Targeting GIRK Channels in Disease.

Authors:  Yulin Zhao; Isabel Gameiro-Ros; Ian W Glaaser; Paul A Slesinger
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Review 9.  GABAergic neurotransmission and new strategies of neuromodulation to compensate synaptic dysfunction in early stages of Alzheimer's disease.

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Journal:  Front Cell Neurosci       Date:  2014-06-25       Impact factor: 5.505

10.  Tethered protein display identifies a novel Kir3.2 (GIRK2) regulator from protein scaffold libraries.

Authors:  Sviatoslav N Bagriantsev; Franck C Chatelain; Kimberly A Clark; Noga Alagem; Eitan Reuveny; Daniel L Minor
Journal:  ACS Chem Neurosci       Date:  2014-07-16       Impact factor: 4.418
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