Structural basis of TRPV3 inhibition by an antagonist

Fan, Junping; Hu, Libo; Yue, Zhihui; Liao, Daohong; Guo, Feng; Ke, Han; Jiang, Dequan; Yong, Yang; Lei, Xiaoguang

doi:10.1038/s41589-022-01166-5

Cited by 16 publications

(20 citation statements)

References 56 publications

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“…TRPV3 antagonist dyclonine improves skin inflammation and abrasions, pain, and pruritus, and is FDA-approved as a topical anesthetic [44]. Trpvicin, a selective TRPV3 antagonist, has been shown to reduce scratching behavior in mice models of acute and chronic pruritus [45]. Furthermore, a recent novel topical small molecular inhibitor of TRPV3 channel (KM001) is currently undergoing phase II trials for lichen simplex chronicus, which is highly associated with keratinocyte itch activation [46].…”

Section: Trp Vanilloid 3 (Trpv3)mentioning

confidence: 99%

Transient Receptor Potential Channels and Itch

Mahmoud

Soares

Yosipovitch

2022

IJMS

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Transient Receptor Potential (TRP) channels are multifunctional sensory molecules that are abundant in the skin and are involved in the sensory pathways of itch, pain, and inflammation. In this review article, we explore the complex physiology of different TRP channels, their role in modulating itch sensation, and their contributions to the pathophysiology of acute and chronic itch conditions. We also cover small molecule and topical TRP channel agents that are emerging as potential anti-pruritic treatments; some of which have shown great promise, with a few treatments advancing into clinical trials—namely, TRPV1, TRPV3, TRPA1, and TRPM8 targets. Lastly, we touch on possible ethnic differences in TRP channel genetic polymorphisms and how this may affect treatment response to TRP channel targets. Further controlled studies on the safety and efficacy of these emerging treatments is needed before clinical use.

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Section: Trp Vanilloid 3 (Trpv3)mentioning

confidence: 99%

Transient Receptor Potential Channels and Itch

Mahmoud

Soares

Yosipovitch

2022

IJMS

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“…Icilin functions as a TRPV3 antagonist, as well as a TRPM8 agonist, and can modulate pain with dual actions [ 61 ]. Trpvicin, a synthetic TRPV3 antagonist, works by inhibiting TRPV3 channels by stabilizing them in the closed state and has been shown to have pharmacological potential to reduce pruritus in mouse models [ 62 ]. We believe that TRPV3 antagonists may be effective therapeutic agents, and further studies should be conducted for drug discovery and development in the future.…”

Section: Therapeutic Potential Of Synthetic Trpv3 Inhibitorsmentioning

confidence: 99%

TRPV3 and Itch: The Role of TRPV3 in Chronic Pruritus according to Clinical and Experimental Evidence

Kim

et al. 2022

IJMS

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Itching is a sensory phenomenon characterized by an unpleasant sensation that makes you want to scratch the skin, and chronic itching diminishes the quality of life. In recent studies, multiple transient receptor potential (TRP) channels present in keratinocytes or nerve endings have been shown to engage in the propagation of itch signals in chronic dermatological or pruritic conditions, such as atopic dermatitis (AD) and psoriasis (PS). TRPV3, a member of the TRP family, is highly expressed in the epidermal keratinocytes. Normal TRPV3 signaling is essential for maintaining epidermal barrier homeostasis. In recent decades, many studies have suggested that TRPV3 contributes to detecting pruritus signals. Gain-of-function mutations in TRPV3 in mice and humans are characterized by severe itching, hyperkeratosis, and elevated total IgE levels. These studies suggest that TRPV3 is an important channel for skin itching. Preclinical studies have provided evidence to support the development of TRPV3 antagonists for treating inflammatory skin conditions, itchiness, and pain. This review explores the role of TRPV3 in chronic pruritus, collating clinical and experimental evidence. We also discuss underlying cellular and molecular mechanisms and explore the potential of TRPV3 antagonists as therapeutic agents.

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“…Members of the transient receptor potential (TRP) superfamily are weakly voltage-dependent, nonselective cation channels, and the more than 30 TRP channels identi ed to date have been shown to have important roles in physiological processes [1,2]. Transient Receptor Potential Vanilloid 4 (TRPV4), isolated from rat kidney, is a widely expressed cation channel that transports cations such as calcium, potassium, magnesium, and sodium, and plays an important role in many physiological and pathological processes [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Establishing a cellular model for drug screening targeting TRPV4

Zheng

Jian

Liu

et al. 2023

Preprint

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Transient receptor potential cation channel subfamily V (TRPV4) is a widely expressed multimodal gated ion channel that transports Ca2+ intracellularly upon opening and plays an important role in many physiological and pathological processes. However, existing TRPV4 channel regulators lack specificity and are ineffective, and available screening methods are not suitable for high-throughput screening of regulators. Therefore, in this study, we developed a cellular model and method for high-throughput drug screening targeting TRPV4 channels based on a double mutant(YFP-H148Q/I152L) of the yellow fluorescent protein (YFP) and the calcium-activated chloride channel protein 1, Anoctamin 1 (ANO1). The endogenous expression of TRPV4 in Fischer Rat Thyroid (FRT) cells was determined, TRPV4 ion channel function in FRT cells was verified by electrophysiological techniques, and a TRPV4 cell model co-expressing ANO1 and YFP-H148Q/I152L was constructed. The model was verified to sensitively detect changes in intracellular Ca2+ concentration using membrane clamp experiments and fluorescence quenching kinetics, and the function of the TRPV4 cell model was examined under different temperatures and concentrations of TRPV4 regulators. The model was evaluated to perform well in high-throughput screening.

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Structural basis of TRPV3 inhibition by an antagonist

Cited by 16 publications

References 56 publications

Transient Receptor Potential Channels and Itch

Transient Receptor Potential Channels and Itch

TRPV3 and Itch: The Role of TRPV3 in Chronic Pruritus according to Clinical and Experimental Evidence

Establishing a cellular model for drug screening targeting TRPV4

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