Inhibition of warm temperature‐sensitive and Ca2+‐permeable TRPV3 channel by a novel compound QDULM‐12 for anti‐pruritus and dermatitis

Abstract

Transient receptor potential vanilloid 3 (TRPV3) channel as a member of thermoTRPV subfamily is primarily expressed in the keratinocytes of the skin and sensory neurons. Genetic gain‐of‐function mutations of TRPV3 gene cause skin‐related diseases such as pruritus and dermatitis, indicating that pharmacological inhibition of overactive TRPV3 may be beneficial for skin health and diseases. However, there is a significant lack of specific tools that can be used to validate TRPV3 channel as therapeutic target for skin diseases or indications yet to be defined. Recently, we made a serial modifications on natural bioactive compound and evaluated their inhibitory activities on human TRPV3 channels expressed in HEK293 cells using whole‐cell patch clamp recordings. We identified a hit compound QDULM‐12 that exhibited a dose‐dependent inhibition of hTRPV3 channel current activated by agonist 2‐APB (50 μM) with an IC50 value in a range of 0.1 μM. The selectivity of QDULM‐12 compound over other thermoTRP channels and its biological effects on in vitro keratinocytes and in vivo pruritus and dermatitis are currently underway.Support or Funding InformationThis work was supported by research grants awarded to XYS from the National Natural Sciences Foundation of China (81903734), the Natural Science Foundation of Shandong Province (ZR2017BH020), and to WKW from the National Natural Sciences Foundation of China (81573410), the Ministry of Science and Technology of China (2018ZX09711001‐004‐006).