2. Academic Validation
  3. Skin- and airway-deliverable TRPA1 inhibitor

Skin- and airway-deliverable TRPA1 inhibitor

  • Bioorg Med Chem. 2024 Jun 24:110:117812. doi: 10.1016/j.bmc.2024.117812.
Tomohiro Shirai 1,  Kazuki Kinoshita 2,  Kentaro Kumihashi 2,  Nanae Mugita 3,  Masahito Yoshida 4,  Hideo Kigoshi 4
Affiliations

Affiliations

  • 1 Sensory Science Research, Kao Corporation, 2606 Akabane, Ichikai-machi, Haga, Tochigi, Japan; Degree Programs in Pure and Applied Sciences, Graduate School of Science and Technology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan. Electronic address: shirai.tomohiro@kao.com.
  • 2 Sensory Science Research, Kao Corporation, 2606 Akabane, Ichikai-machi, Haga, Tochigi, Japan.
  • 3 Safety Science Research, Kao Corporation, 2-1-3 Bunka, Sumida, Tokyo, Japan.
  • 4 Degree Programs in Pure and Applied Sciences, Graduate School of Science and Technology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan.
PMID: 38941887 DOI: 10.1016/j.bmc.2024.117812
Abstract

This study explored the potential of perfumery compounds as sources of transient receptor potential ankyrin 1 (TRPA1) inhibitors that could be formulated for effective delivery to the skin and airways. A highly potent, small, and selective TRPA1 inhibitor, 2-methyl-4-phenyl-1-pentanol (1), was discovered in perfumery compounds. Compound 1 demonstrated promising inhibitory activity against a broad range of TRPA1 agonists. A single stereoisomer of 1 was identified as the most effective TRPA1 inhibitor, indicating the potential for stereoselective synthesis to enhance its potency. Additionally, the structure-activity relationship of 1 was evaluated to elucidate the structural features of TRPA1 inhibitors within the fragrance-like compounds. Notably, the topical application of 1 alleviated sensory irritation in individuals with sensitive skin, while the inhalation of 1 resulted in a significant reduction in ammonia irritation, underscoring its efficacy in both skin and airway applications.

Keywords

Fragrance; Irritation; Odor; Sensitive skin; Structure–activity relationship; TRPA1.

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