Collection of Data Variation Using a High-Throughput Image-Based Assay Platform Facilitates Data-Driven Understanding of TRPA1 Agonist Diversity
Because transient receptor potential ankyrin 1 (TRPA1) is involved in various physiological functions, TRPA1-targeting drugs have been energetically developed. Although TRPA1 is considered a multimodal receptor, the structural diversity of TRPA1 agonists is not fully elucidated. We hypothesized that...
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| Format: | Article |
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MDPI AG
2022-02-01
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| Series: | Applied Sciences |
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| Online Access: | https://www.mdpi.com/2076-3417/12/3/1622 |
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| author | Yuko Terada Kenjiro Tanaka Minami Matsuyama Masaya Fujitani Masatoshi Shibuya Yoshihiko Yamamoto Ryuji Kato Keisuke Ito |
| author_facet | Yuko Terada Kenjiro Tanaka Minami Matsuyama Masaya Fujitani Masatoshi Shibuya Yoshihiko Yamamoto Ryuji Kato Keisuke Ito |
| author_sort | Yuko Terada |
| collection | DOAJ |
| description | Because transient receptor potential ankyrin 1 (TRPA1) is involved in various physiological functions, TRPA1-targeting drugs have been energetically developed. Although TRPA1 is considered a multimodal receptor, the structural diversity of TRPA1 agonists is not fully elucidated. We hypothesized that collecting a wider variation of TRPA1–compound interaction data would aid the understanding of its complex mechanism and aimed to challenge such data collection using an “image-based TRPA1 assay system combined with an in silico chemical space clustering concept.” Our library was clustered with 27 physicochemical molecular descriptors in silico, and structurally diverse compounds from each cluster were selected for a detailed kinetic assay to investigate variations of agonist structural rules. Through two sets of assays evaluating various compounds in parallel with validating effects of the previously established structural rules, we discovered that different chemical groups contribute to agonist activity, indicating that there are multiple agonist design concepts. A novel core structure for a TRPA1 agonist has been also proposed. Our new approach, “collection of TRPA1 activity data on compounds with physicochemical diversity,” will not only facilitate the understanding of the structural diversity of TRPA1 agonists but also contribute to the development of a new type of TRPA1-targeting drug. |
| first_indexed | 2024-03-10T00:10:04Z |
| format | Article |
| id | doaj.art-61d3e943af70426fab93cf21327d6c04 |
| institution | Directory Open Access Journal |
| issn | 2076-3417 |
| language | English |
| last_indexed | 2024-03-10T00:10:04Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Applied Sciences |
| spelling | doaj.art-61d3e943af70426fab93cf21327d6c042023-11-23T16:00:42ZengMDPI AGApplied Sciences2076-34172022-02-01123162210.3390/app12031622Collection of Data Variation Using a High-Throughput Image-Based Assay Platform Facilitates Data-Driven Understanding of TRPA1 Agonist DiversityYuko Terada0Kenjiro Tanaka1Minami Matsuyama2Masaya Fujitani3Masatoshi Shibuya4Yoshihiko Yamamoto5Ryuji Kato6Keisuke Ito7Department of Food and Nutritional Sciences, Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, JapanDepartment of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University, Tokai National Higher Education and Research System, Furocho, Chikusa-ku, Nagoya 464-8601, JapanDepartment of Food and Nutritional Sciences, Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, JapanDepartment of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University, Tokai National Higher Education and Research System, Furocho, Chikusa-ku, Nagoya 464-8601, JapanDepartment of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University, Tokai National Higher Education and Research System, Furocho, Chikusa-ku, Nagoya 464-8601, JapanDepartment of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University, Tokai National Higher Education and Research System, Furocho, Chikusa-ku, Nagoya 464-8601, JapanDepartment of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University, Tokai National Higher Education and Research System, Furocho, Chikusa-ku, Nagoya 464-8601, JapanDepartment of Food and Nutritional Sciences, Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, JapanBecause transient receptor potential ankyrin 1 (TRPA1) is involved in various physiological functions, TRPA1-targeting drugs have been energetically developed. Although TRPA1 is considered a multimodal receptor, the structural diversity of TRPA1 agonists is not fully elucidated. We hypothesized that collecting a wider variation of TRPA1–compound interaction data would aid the understanding of its complex mechanism and aimed to challenge such data collection using an “image-based TRPA1 assay system combined with an in silico chemical space clustering concept.” Our library was clustered with 27 physicochemical molecular descriptors in silico, and structurally diverse compounds from each cluster were selected for a detailed kinetic assay to investigate variations of agonist structural rules. Through two sets of assays evaluating various compounds in parallel with validating effects of the previously established structural rules, we discovered that different chemical groups contribute to agonist activity, indicating that there are multiple agonist design concepts. A novel core structure for a TRPA1 agonist has been also proposed. Our new approach, “collection of TRPA1 activity data on compounds with physicochemical diversity,” will not only facilitate the understanding of the structural diversity of TRPA1 agonists but also contribute to the development of a new type of TRPA1-targeting drug.https://www.mdpi.com/2076-3417/12/3/1622TRPA1 agonistimage-based assayCa<sup>2+</sup> imagingchemical libraryphysicochemical descriptorsclustering |
| spellingShingle | Yuko Terada Kenjiro Tanaka Minami Matsuyama Masaya Fujitani Masatoshi Shibuya Yoshihiko Yamamoto Ryuji Kato Keisuke Ito Collection of Data Variation Using a High-Throughput Image-Based Assay Platform Facilitates Data-Driven Understanding of TRPA1 Agonist Diversity Applied Sciences TRPA1 agonist image-based assay Ca<sup>2+</sup> imaging chemical library physicochemical descriptors clustering |
| title | Collection of Data Variation Using a High-Throughput Image-Based Assay Platform Facilitates Data-Driven Understanding of TRPA1 Agonist Diversity |
| title_full | Collection of Data Variation Using a High-Throughput Image-Based Assay Platform Facilitates Data-Driven Understanding of TRPA1 Agonist Diversity |
| title_fullStr | Collection of Data Variation Using a High-Throughput Image-Based Assay Platform Facilitates Data-Driven Understanding of TRPA1 Agonist Diversity |
| title_full_unstemmed | Collection of Data Variation Using a High-Throughput Image-Based Assay Platform Facilitates Data-Driven Understanding of TRPA1 Agonist Diversity |
| title_short | Collection of Data Variation Using a High-Throughput Image-Based Assay Platform Facilitates Data-Driven Understanding of TRPA1 Agonist Diversity |
| title_sort | collection of data variation using a high throughput image based assay platform facilitates data driven understanding of trpa1 agonist diversity |
| topic | TRPA1 agonist image-based assay Ca<sup>2+</sup> imaging chemical library physicochemical descriptors clustering |
| url | https://www.mdpi.com/2076-3417/12/3/1622 |
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