The design and synthesis of transient receptor potential vanilloid 3 inhibitors with novel skeleton

Abstract

Transient receptor potential vanilloid 3 (TRPV3) channel as a member of thermo TRPV subfamily is primarily expressed in the keratinocytes of the skin and sensory neurons, and plays critical roles in various physiological and pathological processes such as inflammation, pain sensation and skin disorders. However, TRPV3 studies have been challenging, in part due to a lack of research tools such as selective antagonists. Recently, we synthesized a series of cinnamate ester derivatives and evaluated their inhibitory activities on human TRPV3 channels expressed in HEK293 cells using whole-cell patch clamp recordings. And, we identified two potent TRPV3 antagonists 7c and 8c which IC₅₀ values were 1.05 μM and 86 nM, respectively. It also showed good selectivity to other subfamily members of TRPV, such as TRPV1 and TRPV4.

Keywords: Inhibitor; Selectivity; Small molecular; TRPV3.