Hiroshi Nagase

Affiliation:International Institute for Integrative Sleep Medicine, University of Tsukuba

Research Title

Drug discovery

Drug design and synthetic studies targeting on orexin and opioid receptors

01 Research Summary

Our main work is drug discovery and development at university. Our primary target compound is the orexin receptor agonists. So far we succeeded in the design and synthesis of the first orexin 2 receptor selective agonists in the world, and we are collaborating with Merck&Co., Inc. In the near future, we will grow the compound to a silver-bullet to cure sleep disorders, such as narcolepsy. We are also studying the orexin 1 receptor antagonists as the drug for the drug addiction patients. We are also studying on opioid (morphine-like compounds). One of the most famous opioid is morphine which shows strong analgesic effects, but also serious side effects, addiction, respiratory suppression, and constipation. Recently, we released opioid receptor agonist nalfurafine as a non-addictive antipruritic drug for kidney dialysis patients. Additionally, many projects to develop the drugs for many diseases such as depression, anxiety, cancer and adiposity are ongoing at our lab.

Nagase Laboratory

Nagase Laboratory

02 Major achievements

Nagase, H.; Yamamoto, N.; Yata, M.; Ohrui, S.; Okada, T.; Saitoh, T.; Kutsumura, N.; Nagumo, Y.; Irukayama-Tomobe, Y.; Ishikawa, Y.; Ogawa, Y.; Hirayama, S.; Kuroda, D.; Watanabe, Y.; Gouda, H.; Yanagisawa, M. “Design and Synthesis of Potent and Highly Selective Orexin 1 Receptor Antagonists with a Morphinan Skeleton and their Pharmacologies” J. Med. Chem. 2017, 60, 1018–1040.

Nagahara, T.; Saitoh, T.; Kutsumura, N.; Irukayama-Tomobe, Y.; Ogawa, Y.; Kuroda, D.; Gouda, H.; Kumagai, H.; Fujii, H.; Yanagisawa, M.; Nagase, H. “Design and Synthesis of Non-Peptide, Selective Orexin Receptor 2 Agonists” J. Med. Chem. 2015, 58, 7931–7937.

Kawai, K.; Hayakawa, J.; Miyamoto, T.; Imamura, Y.; Yamane, S.; Wakita, H.; Fujii, H.; Kawamura, K.; Matsuura, H.; Izumimoto, N.; Kobayashi, R.; Endo, T.; Nagase, H. “Design, synthesis, and structure–activity relationship of novel opioid κ-agonists” Bioorg. Med. Chem. 2008, 16, 9188–9201.

03 Education/Academic background and major awards

Education/Academic background

1978 Ph.D. Nagoya University
1985-1987 Postdoctoral fellow, University of Minnesota
2001-2004 Director, Toray Pharmaceutical Research laboratories
2004-2012 Professor, Kitazato University of Pharmacy
2013 Present Professor, International Institute for Integrative Sleep Medicine, University of Tsukuba
2014 Present Professor, Graduate School of Comprehensive Human Sciences, University of Tsukuba Professor, Graduate School of Pure and Applied Sciences, University of Tsukuba
2015 Present Professor, Master’s/Doctoral Program in Life Science Innovation, University of Tsukuba


1995, 2013 Ookochi Memorial Technology Prize
1996, 2013 Synthetic Organic Chemistry Award, Japan
1997 Patent Attorney Award, Japan on The National Commendation of Invention
1998, 2009 Drug-Discovery Science Award, Japan
2013 The Invention Prize, Japan on The National Commendation of Invention
2014 The Yamazaki Teiichi Prize


Why did you become a scientist?

I always thought that I wanted to be a worldwide scientist.

My first interest in the organic chemistry was the chemical experiment in my second year of high school. The experiments afforded new compounds by mixing some materials, which stimulated my interests to the endless possibilities of “creating something new”. On my fourth year, I joined the research group of Professor. Yoshimasa Hirata at Nagoya University, who was a famous scientist who determined the structure of the tetrodotoxin isolated from puffer fish. The laboratory threw up famous professors at outstanding universities, such as Harvard and Colombia. They were hard-workers and kept studying even on Sunday and late at night. We were spontaneously trained at the tough environment to become worldwide scientists.

What are the characteristics of your lab?

We can “discover drugs and release it to the market.”

We design and synthesized the drugs by use of medicinal chemistry and organic chemistry for our greatest mission: “discover drugs and send them to the market.” Both abilities to “design and synthesize compounds and the resulting drug candidates and to “evaluate the activities of the resulting drug candidates are necessary. Furthermore, the optimization by using structure-activity relationship studies would are effective. Researchers at our lab must study not only synthetic organic chemistry, but also medicinal chemistry, pharmacy, biochemistry, molecular biology, pharmacology, pharmacokinetics and pharmaceutics. We provide opportunities to learn and obtain the knowledge through our research activities. Students at our lab. will be able to obtain sufficient experience and research abilities at the pharmaceutical company upon completion of their degrees.

What are you most interested in lately


I love wine and I sometimes host wine parties. To tell the truth, I never felt them to be delicious before my 50s, but a California wine called Opus One changed my life. It was so delicious and I started trying out different kinds wines in the world ever since. I even tasted Bordeaux that costs over a million yen. Most wine over 10 years and 10 thousand yen would be delicious. The oldest wines I own were produced in 1947 and 1952, which are my and my wife’s birth years. I wonder when to open them.