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

Zelin Hu; Ya Zhang; Wenhan Yu; Junjie Li; Jiaqi Yao; Jifa Zhang; Jiaxing Wang; Chengdi Wang

doi:10.1016/j.ejmech.2023.115392

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

Eur J Med Chem. 2023 Sep 5:257:115392. doi: 10.1016/j.ejmech.2023.115392. Epub 2023 May 18.

Authors

Zelin Hu¹, Ya Zhang¹, Wenhan Yu², Junjie Li³, Jiaqi Yao¹, Jifa Zhang³, Jiaxing Wang⁴, Chengdi Wang⁵

Affiliations

¹ Department of Pulmonary and Critical Care Medicine, Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China; Precision Medicine Key Laboratory of Sichuan Province & Precision Medicine Research Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China; College of Life Sciences, Sichuan University, Chengdu, 610064, China.
² College of Letters & Science, University of California, Berkeley, Berkeley, 94720, California, United States.
³ Department of Pulmonary and Critical Care Medicine, Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China; Precision Medicine Key Laboratory of Sichuan Province & Precision Medicine Research Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
⁴ Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, 38163, Tennessee, United States.
⁵ Department of Pulmonary and Critical Care Medicine, Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China. Electronic address: chengdi_wang@scu.edu.cn.

PMID: 37269667
DOI: 10.1016/j.ejmech.2023.115392

Abstract

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.

Keywords: Agonists; Antagonists; Ion channel; TRPA1.

Publication types

Review

MeSH terms

Ankyrins / metabolism
Cytoskeletal Proteins / metabolism
TRPA1 Cation Channel / metabolism
Transient Receptor Potential Channels* / metabolism

Substances

Transient Receptor Potential Channels
TRPA1 Cation Channel
Ankyrins
Cytoskeletal Proteins