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TRP Channels in Drug Discovery pp 257–270Cite as

TRPV4 and Drug Discovery

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Part of the book series: Methods in Pharmacology and Toxicology ((MIPT))

Abstract

Transient receptor potential vanilloid 4 (TRPV4) was first identified in 2000 as an osmolarity sensor. Further investigations rapidly revealed this ion channel to be a polymodal receptor with additional activating or modulating stimuli including warm temperatures, endogenous lipids, and phosphorylation. The broad tissue and cell type distribution of TRPV4, coupled with its varied activation profile, lead to a wide variety of physiological roles. These include sheer stress detection in blood vessels, osteoclast differentiation control in bone, along with temperature monitoring in skin keratinocytes and osmolarity sensing in kidneys. Recent work has also implicated TRPV4 mutations in multiple genetic disorders such as brachyolmia and Charcot–Marie–Tooth disease 2C. Characterization of its roles in disease states naturally led to a rising interest in the modulation of TRPV4 for therapeutic purposes. Therapeutic areas of interest are diverse and include several with significant unmet medical needs such as inflammatory and neuropathic pain, bladder dysfunctions, as well as mechanical lung injury. Herein we review the roles of TRPV4 in pathologies and summarize the progress made in identifying small molecule modulators of its activity for target validation and therapeutic purposes.

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Authors and Affiliations

  1. Pfizer, Inc., Groton, CT, USA

    Fabien Vincent

  2. Formerly with Renovis, Inc. (a wholly owned subsidiary of Evotec AG), South San Francisco, CA, USA

    Matthew A. J. Duncton

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  1. Fabien Vincent
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  2. Matthew A. J. Duncton
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Correspondence to Fabien Vincent .

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Editors and Affiliations

  1. , Transfusion Services, Monmouth Medical Center, Second Avenue 300, Long Branch, 07740, New Jersey, USA

    Arpad Szallasi

  2. Medical and Health Science Center, Department of Physiology, University of Debrecen, Nagyerdei Krt. 98, Debrecen, 4032, Hungary

    Tamás Bíró

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Vincent, F., Duncton, M.A.J. (2012). TRPV4 and Drug Discovery. In: Szallasi, A., Bíró, T. (eds) TRP Channels in Drug Discovery. Methods in Pharmacology and Toxicology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-077-9_13

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  • DOI: https://doi.org/10.1007/978-1-62703-077-9_13

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