Literature DB >> 26235950

Identification of orally-bioavailable antagonists of the TRPV4 ion-channel.

Zhi-Liang Wei1, Margaret T Nguyen1, Donogh J R O'Mahony1, Alejandra Acevedo1, Sheila Zipfel1, Qingling Zhang1, Luna Liu1, Michelle Dourado1, Candace Chi1, Victor Yip1, Jeff DeFalco1, Amy Gustafson1, Daniel E Emerling1, Michael G Kelly1, John Kincaid1, Fabien Vincent2, Matthew A J Duncton3.   

Abstract

Antagonists of the TRPV4 receptor were identified using a focused screen, followed by a limited optimization program. The leading compounds obtained from this exercise, RN-1665 23 and RN-9893 26, showed moderate oral bioavailability when dosed to rats. The lead molecule, RN-9893 26, inhibited human, rat and murine variants of TRPV4, and showed excellent selectivity over related TRP receptors, such as TRPV1, TRPV3 and TRPM8. The overall profile for RN-9893 may permit its use as a proof-of-concept probe for in vivo applications.
Copyright © 2015 Elsevier Ltd. All rights reserved.

Entities:  

Keywords:  Antagonist; Pain; RN-1734; RN-9893; TRPV4

Mesh：

Substances：

Year:  2015        PMID： 26235950     DOI： 10.1016/j.bmcl.2015.06.098

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


  10 in total

1.  Transient receptor potential channel TRPV4 mediates TGF-β1-induced differentiation of human ventricular fibroblasts.

Authors:  Min-Soo Ahn; Young Woo Eom; Ji-Eun Oh; Seung-Kuy Cha; Kyu Sang Park; Jung-Woo Son; Jun-Won Lee; Young Jin Youn; Sung Gyun Ahn; Jang-Young Kim; Seung-Hwan Lee; Junghan Yoon; Byung-Su Yoo
Journal:  Cardiol J       Date:  2020-04-24       Impact factor: 2.737

Review 2.  Calcium signals that determine vascular resistance.

Authors:  Matteo Ottolini; Kwangseok Hong; Swapnil K Sonkusare
Journal:  Wiley Interdiscip Rev Syst Biol Med       Date:  2019-03-18

3.  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

4.  Ion channel mediated mechanotransduction in immune cells.

Authors:  Atcha Hamza; Jairaman Amit; Evans Elizabeth L; Pathak Medha M; Cahalan Michael D; Liu Wendy F
Journal:  Curr Opin Solid State Mater Sci       Date:  2021-09-15       Impact factor: 12.857

Review 5.  Novel Pharmacological Nonopioid Therapies in Chronic Pain.

Authors:  Alan David Kaye; Elyse M Cornett; Brendon Hart; Shilpadevi Patil; Andrew Pham; Matthew Spalitta; Kenneth F Mancuso
Journal:  Curr Pain Headache Rep       Date:  2018-04-03

6.  MiR-29a Suppresses Spermatogenic Cell Apoptosis in Testicular Ischemia-Reperfusion Injury by Targeting TRPV4 Channels.

Authors:  Jin-Zhuo Ning; Wei Li; Fan Cheng; Wei-Min Yu; Ting Rao; Yuan Ruan; Run Yuan; Xiao-Bin Zhang; Dong Zhuo; Yang Du; Cheng-Cheng Xiao
Journal:  Front Physiol       Date:  2017-11-29       Impact factor: 4.566

7.  Picomolar, selective, and subtype-specific small-molecule inhibition of TRPC1/4/5 channels.

Authors:  Hussein N Rubaiy; Melanie J Ludlow; Matthias Henrot; Hannah J Gaunt; Katarina Miteva; Sin Ying Cheung; Yasuyuki Tanahashi; Nurasyikin Hamzah; Katie E Musialowski; Nicola M Blythe; Hollie L Appleby; Marc A Bailey; Lynn McKeown; Roger Taylor; Richard Foster; Herbert Waldmann; Peter Nussbaumer; Mathias Christmann; Robin S Bon; Katsuhiko Muraki; David J Beech
Journal:  J Biol Chem       Date:  2017-03-21       Impact factor: 5.157

Review 8.  Targeting calcium signaling in cancer therapy.

Authors:  Chaochu Cui; Robert Merritt; Liwu Fu; Zui Pan
Journal:  Acta Pharm Sin B       Date:  2016-12-13       Impact factor: 11.413

9.  Nuclear decoupling is part of a rapid protein-level cellular response to high-intensity mechanical loading.

Authors:  Hamish T J Gilbert; Venkatesh Mallikarjun; Oana Dobre; Mark R Jackson; Robert Pedley; Andrew P Gilmore; Stephen M Richardson; Joe Swift
Journal:  Nat Commun       Date:  2019-09-12       Impact factor: 14.919

10.  Expression and function of mechanosensitive ion channels in human valve interstitial cells.

Authors:  Hessah Al-Shammari; Najma Latif; Padmini Sarathchandra; Ann McCormack; Eva A Rog-Zielinska; Shahzad Raja; Peter Kohl; Magdi H Yacoub; Rémi Peyronnet; Adrian H Chester
Journal:  PLoS One       Date:  2020-10-15       Impact factor: 3.240
  10 in total

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