National University Corporation Okayama University
[Okayama University] Successfully developed an inhibitor against AAK1, which is involved in various neurological disorders! – Expected to be applied to rapid drug discovery cycle by method using existing inhibitors –
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May 9, 2024 (Reiwa 6) National University Corporation Okayama University https://www.okayama-u.ac.jp/
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-Key points of presentation-
Protein kinase is an enzyme that controls intracellular information transmission mechanisms and is involved in various diseases including cancer, and many inhibitors targeting this enzyme have been approved by the U.S. Food and Drug Administration as therapeutic drugs. It is approved as.
By using existing kinase inhibitors, we succeeded in developing a selective inhibitor of a new kinase, Adaptor Protein 2-Associated Kinase 1 (AAK1).
The new inhibitor development method, which begins with the
identification of enzymes that interact with kinase inhibitors, is expected to be applied to rapid drug discovery cycles that target protein kinases as molecular targets.
◆Summary National University Corporation Okayama University
(Headquarters: Kita-ku, Okayama City, President: Yasutomo Nasu) The research group of Professor Hiroshi Tokumitsu of the Faculty of Health System Integration Science and the research group of Professor Akihiko Ishikawa of the Faculty of Education, Faculty of Academic Research. The research group was developed through international collaborative research with Associate Professor Ayano Sato of the Faculty of Health System Integrative Sciences, Associate Professor Yukinari Sunatsuki of the Natural Life Sciences Research Support Center, and Professor Ulf J. Nilsson of Lund University in Sweden. By using proteomics, synthetic organic chemistry, biochemistry, cell biology, and molecular docking simulations, we succeeded in developing a new selective inhibitor of the protein kinase AAK1 from existing protein kinase inhibitors.
The results of this research demonstrate not only the possibility of application to therapeutic drugs for neuropathic pain and various viral infections that are thought to be related to AAK1, but also the fact that this method for developing kinase inhibitors is costly and time-consuming. It is expected that this method will be useful in drug discovery and development.
The results of this research were published online in the
international academic journal “Scientific Reports” on March 20, 2024. This matter was published by Okayama University on April 24, 2024.
[Image 2: https://prtimes.jp/i/72793/2191/resize/d72793-2191-a532fbd1e431bc98b7ac-1.jpg&s3=72793-2191-a7876f0788b65981caefd2bd1160940c-732×1210.jpg] ◆A word from the researchers
This is a multidisciplinary research result achieved by bringing together domestic and international researchers and graduate students with various research and analysis methods and specialized fields, from organic synthetic chemistry, enzymology, cell biology to computer simulation. It was a very exciting time. We hope that this research will accelerate drug discovery and development.
[Image 3: https://prtimes.jp/i/72793/2191/resize/d72793-2191-9ac1319683aed53eb3ec-2.jpg&s3=72793-2191-346672e3693a1ca49988d700da3152a6-1208×640.jpg] Research team members of Professor Tokumitsu (far left) and Professor Ishikawa (far right) who were involved in this research
◆Paper information Paper title: Development of a novel AAK1 inhibitor via Kinobeads-based screening Publication paper: Scientific Reports Author: Akari Yoshida, Satomi Ohtsuka, Fumiya Matsumoto, Tomoyuki Miyagawa, Rei Okino, Yumeya Ikeda, Natsume Tada, Akira Gotoh , Masaki Magari, Naoya Hatano, Ryo Morishita, Ayano Satoh, Yukinari Sunatsuki, Ulf J. Nilsson, Teruhiko Ishikawa, Hiroshi Tokumitsu D O I:
10.1038/s41598-024-57051-9 U R L: https://www.nature.com/articles /s41598-024-57051-9
◆Research Funding This research was supported by the Grant-in-Aid for Scientific Research (JP21H02429) and the Sanyo Broadcasting Academic Culture and Sports Foundation Academic Research Grant.
◆Detailed research details Succeeded in developing an inhibitor against AAK1, which is involved in various neurological disorders! – Expected to be applied to rapid drug discovery cycle by method using existing inhibitors –
https://www.okayama-u.ac.jp/up_load_files/press_r6/press20240424-9.pdf ◆Reference
・Department of Cell Function Design, Graduate School of Health System Integrative Sciences, Okayama University
https://www.okayama-u.ac.jp/user/saibou/
・Okayama University Graduate School of Education, Department of Natural Education, Science Education Course
https://edu.okayama-u.ac.jp/~rika/sci-home/people.html
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Hiroshi Tokumitsu, Professor, Department of Biotechnology and Drug Discovery, Faculty of Health Systems, Faculty of Academic Research, Okayama University 3-1-1 Tsushima Naka, Kita-ku, Okayama City, Okayama Prefecture 700-8530 Okayama University Tsushima Campus
TEL: 086-251-8197
FAX: 086-251-8197
https://www.okayama-u.ac.jp/user/saibou/ Okayama University Faculty of Academic Research, Department of Education, Professor Akihiko Ishikawa
3-1-1 Tsushima Naka, Kita-ku, Okayama City, Okayama Prefecture 700-8530 Okayama University Tsushima Campus TEL: 086-251-7639 FAX: 086-251-7639
https://edu.okayama-u.ac.jp/~rika/sci-home/people.html
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