Literature DB >> 24900661

Optimization of a Novel Series of TRPV4 Antagonists with In Vivo Activity in a Model of Pulmonary Edema.

Mark A Hilfiker1, Tram H Hoang1, Johan Cornil1, Hilary S Eidam1, Daniel S Matasic1, Theresa J Roethke1, Michael Klein2, Kevin S Thorneloe1, Mui Cheung1.   

Abstract

High-throughput screening and subsequent hit optimization identified 1-piperidinylbenzimidazoles, exemplified by compound 1, as TRPV4 inhibitors. Lead optimization identified potent TRPV4 blocker 19, which has good target activity and pharmacokinetic properties. Inhibitor 19 was then profiled in an in vivo rat model, demonstrating its ability to inhibit TRPV4-mediated pulmonary edema.

Entities:  

Keywords:  TRPV4; benzimidazole; calcium channel; heart failure; ion channel; pulmonary edema; transient receptor potential; vanilloid receptor

Year:  2013        PMID： 24900661      PMCID： PMC4027501          DOI： 10.1021/ml300449k

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


  11 in total

1.  Pressure-induced endothelial Ca(2+) oscillations in lung capillaries.

Authors:  Wolfgang M Kuebler; Xiaoyou Ying; Jahar Bhattacharya
Journal:  Am J Physiol Lung Cell Mol Physiol       Date:  2002-05       Impact factor: 5.464

Review 2.  The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination.

Authors:  G R Bernard; A Artigas; K L Brigham; J Carlet; K Falke; L Hudson; M Lamy; J R Legall; A Morris; R Spragg
Journal:  Am J Respir Crit Care Med       Date:  1994-03       Impact factor: 21.405

Review 3.  TRPV4 agonists and antagonists.

Authors:  Fabien Vincent; Matthew A J Duncton
Journal:  Curr Top Med Chem       Date:  2011       Impact factor: 3.295

Review 4.  Future research directions in acute lung injury: summary of a National Heart, Lung, and Blood Institute working group.

Authors:  Michael A Matthay; Guy A Zimmerman; Charles Esmon; Jahar Bhattacharya; Barry Coller; Claire M Doerschuk; Joanna Floros; Michael A Gimbrone; Eric Hoffman; Rolf D Hubmayr; Mark Leppert; Sadis Matalon; Robert Munford; Polly Parsons; Arthur S Slutsky; Kevin J Tracey; Peter Ward; Dorothy B Gail; Andrea L Harabin
Journal:  Am J Respir Crit Care Med       Date:  2003-04-01       Impact factor: 21.405

5.  Transient receptor potential vanilloid 4-mediated disruption of the alveolar septal barrier: a novel mechanism of acute lung injury.

Authors:  Diego F Alvarez; Judy A King; David Weber; Emile Addison; Wolfgang Liedtke; Mary I Townsley
Journal:  Circ Res       Date:  2006-09-28       Impact factor: 17.367

6.  TRPV4-mediated endothelial Ca2+ influx and vasodilation in response to shear stress.

Authors:  Suelhem A Mendoza; Juan Fang; David D Gutterman; David A Wilcox; Aaron H Bubolz; Rongshan Li; Makoto Suzuki; David X Zhang
Journal:  Am J Physiol Heart Circ Physiol       Date:  2009-12-04       Impact factor: 4.733

Review 7.  The vanilloid transient receptor potential channel TRPV4: from structure to disease.

Authors:  Wouter Everaerts; Bernd Nilius; Grzegorz Owsianik
Journal:  Prog Biophys Mol Biol       Date:  2009-10-14       Impact factor: 3.667

8.  High vascular pressure-induced lung injury requires P450 epoxygenase-dependent activation of TRPV4.

Authors:  Ming-Yuan Jian; Judy A King; Abu-Bakr Al-Mehdi; Wolfgang Liedtke; Mary I Townsley
Journal:  Am J Respir Cell Mol Biol       Date:  2007-10-25       Impact factor: 6.914

9.  Systemic activation of the transient receptor potential vanilloid subtype 4 channel causes endothelial failure and circulatory collapse: Part 2.

Authors:  Robert N Willette; Weike Bao; Sandhya Nerurkar; Tian-Li Yue; Chris P Doe; Gerald Stankus; Gregory H Turner; Haisong Ju; Heath Thomas; Cindy E Fishman; Anthony Sulpizio; David J Behm; Sandra Hoffman; Zuojun Lin; Irina Lozinskaya; Linda N Casillas; Min Lin; Robert E Lee Trout; Bartholomew J Votta; Kevin Thorneloe; Erin S R Lashinger; David J Figueroa; Robert Marquis; Xiaoping Xu
Journal:  J Pharmacol Exp Ther       Date:  2008-05-22       Impact factor: 4.030

10.  An orally active TRPV4 channel blocker prevents and resolves pulmonary edema induced by heart failure.

Authors:  Kevin S Thorneloe; Mui Cheung; Weike Bao; Hasan Alsaid; Stephen Lenhard; Ming-Yuan Jian; Melissa Costell; Kristeen Maniscalco-Hauk; John A Krawiec; Alan Olzinski; Earl Gordon; Irina Lozinskaya; Lou Elefante; Pu Qin; Daniel S Matasic; Chris James; James Tunstead; Brian Donovan; Lorena Kallal; Anna Waszkiewicz; Kalindi Vaidya; Elizabeth A Davenport; Jonathan Larkin; Mark Burgert; Linda N Casillas; Robert W Marquis; Guosen Ye; Hilary S Eidam; Krista B Goodman; John R Toomey; Theresa J Roethke; Beat M Jucker; Christine G Schnackenberg; Mary I Townsley; John J Lepore; Robert N Willette
Journal:  Sci Transl Med       Date:  2012-11-07       Impact factor: 17.956
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  6 in total

1.  Genetic deficit of KCa 3.1 channels protects against pulmonary circulatory collapse induced by TRPV4 channel activation.

Authors:  Christine Wandall-Frostholm; Thomas Dalsgaard; Vytis Bajoriūnas; Aida Oliván-Viguera; Veeruanjaneyulu Sadda; Lilliana Beck; Susie Mogensen; Edgaras Stankevicius; Ulf Simonsen; Ralf Köhler
Journal:  Br J Pharmacol       Date:  2015-07-24       Impact factor: 8.739

2.  Discovery of GSK2193874: An Orally Active, Potent, and Selective Blocker of Transient Receptor Potential Vanilloid 4.

Authors:  Mui Cheung; Weike Bao; David J Behm; Carl A Brooks; Michael J Bury; Sarah E Dowdell; Hilary S Eidam; Ryan M Fox; Krista B Goodman; Dennis A Holt; Dennis Lee; Theresa J Roethke; Robert N Willette; Xiaoping Xu; Guosen Ye; Kevin S Thorneloe
Journal:  ACS Med Chem Lett       Date:  2017-03-20       Impact factor: 4.345

3.  Discovery of GSK2798745: A Clinical Candidate for Inhibition of Transient Receptor Potential Vanilloid 4 (TRPV4).

Authors:  Carl A Brooks; Linda S Barton; David J Behm; Hilary S Eidam; Ryan M Fox; Marlys Hammond; Tram H Hoang; Dennis A Holt; Mark A Hilfiker; Brian G Lawhorn; Jaclyn R Patterson; Patrick Stoy; Theresa J Roethke; Guosen Ye; Steve Zhao; Kevin S Thorneloe; Krista B Goodman; Mui Cheung
Journal:  ACS Med Chem Lett       Date:  2019-07-15       Impact factor: 4.345

Review 4.  Applications of Palladium-Catalyzed C-N Cross-Coupling Reactions.

Authors:  Paula Ruiz-Castillo; Stephen L Buchwald
Journal:  Chem Rev       Date:  2016-09-30       Impact factor: 60.622

5.  The Resting Potential and K+ Currents in Primary Human Articular Chondrocytes.

Authors:  Mary M Maleckar; Robert B Clark; Bartholomew Votta; Wayne R Giles
Journal:  Front Physiol       Date:  2018-09-04       Impact factor: 4.566

6.  Design, Synthesis and In Vitro Experimental Validation of Novel TRPV4 Antagonists Inspired by Labdane Diterpenes.

Authors:  Sarah Mazzotta; Gabriele Carullo; Aniello Schiano Moriello; Pietro Amodeo; Vincenzo Di Marzo; Margarita Vega-Holm; Rosa Maria Vitale; Francesca Aiello; Antonella Brizzi; Luciano De Petrocellis
Journal:  Mar Drugs       Date:  2020-10-18       Impact factor: 5.118
  6 in total

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