ArticleCurrent pharmaceutical design2025
Identification of Novel Selective Transient Receptor Potential Vanilloid 4 (TRPV4) Agonists.
Article in Current pharmaceutical design, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
aimsWe aimed to synthesize small-molecule compounds by modifying the chemical structure of GSK101 and screening for novel TRPV4 agonists with high specificity and selective sensory response.
backgroundGSK1016790A (GSK101) effectively activates Transient Receptor Potential Vanilloid 4 (TRPV4) and simultaneously induces mechanical allodynia and acute itch. However, as a commonly used tool compound for studying sensory function, its dual effects of pain and itch can interfere with each other.
objectiveTo design and synthesize a series of small-molecule compounds targeting TRPV4, evaluate their properties to identify the most specific tool compounds targeting TRPV4, and determine the correlation between TRPV4 activation and sensory response.
methodsIn this study, live-cell Ca
resultsWe synthesized nine GSK101 analogues and identified six small-molecule agonists that exhibited TRPV4- targeting excitability, preserved TRPV4-mediated mechanical pain perception, and attenuated the acute itch response.
conclusionOur study provides new insight into the role of TRPV4 in pain and itch sensation and introduces LM0038, the most potent agonist, as a novel alternative to GSK101. With enhanced biological activity, it may serve as a valuable tool for studying TRPV4 function.
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