Transient receptor potential ankyrin 1 (TRPA1) modulators: Recent update and future perspective

The transient receptor potential ankyrin 1 (TRPA1) channel is a non-selective cation channel that senses irritant chemicals. Its activation is closely associated with pain, inflammation, and pruritus. TRPA1 antagonists are promising treatments for these diseases, and there has been a recent upsurge in their application to new areas such as cancer, asthma, and Alzheimer's disease. However, due to the generally disappointing performance of TRPA1 antagonists in clinical studies, scientists must pursue the development of antagonists with higher selectivity, metabolic stability, and solubility. Moreover, TRPA1 agonists provide a deeper understanding of activation mechanisms and aid in antagonist screening. Therefore, we summarize the TRPA1 antagonists and agonists developed in recent years, with a particular focus on structure-activity relationships (SARs) and pharmacological activity. In this perspective, we endeavor to keep abreast of cutting-edge ideas and provide inspiration for the development of more effective TRPA1-modulating drugs. [Display omitted] •TRPA1 plays a key role in somatosensation by acting as a sensor of thermal and chemical stimuli.•TRPA1 antagonists have great potential in the treatment of pain, inflammation, pruritus, asthma, and Alzheimer's disease.•Systematic collation on TRPA1 agonists and antagonists developed in recent years.•Elaboration of SARs, pharmacological activity, source ideas, structures, and their modifications.