We are engaged in the design and synthesis of orexin receptor agonists,
and also opioid research in WPI-IIIS, University of Tsukuba.


Our fundamental field of science is Medicinal Chemistry.

Prof. Nagase et al. (Toray Ind., Inc.) released the first orally-active PGI2 derivative in the world, Dorner®, in 1992 (indication: peripheral circulation disorder and pulmonary hypertension), and then also released the first selective κ opioid receptor agonist in the world, Remitch® Capsules in 2009 (indication: severe itch in hemodialysis patients). In this institute (WPI-IIIS), we are going to design and synthesize agonists utilizing the experience and know-how obtained in the course of the research processes, and the basic technologies of organic chemistry.

Application Of Technology

First, our research target compounds are orexin receptor agonists, which are related with sleep/wake switching, eating and emotion behavior. Creation of such non-peptide small molecules as alternatives for the hypothalamic neuropeptide orexin would lead to a drug for sleep disorders, such as narcolepsy. In addition, the orexin receptor is considered to be related with eating and emotional behavior, thus the research development of not only agonists but antagonists is expected to be useful for clarifying the mechanism of eating behavior, depressant and anxiety symptoms.

Orexin like-activity

To release a “First-in-class Drug” to the market, we have to design and synthesize drug-like compounds and evaluate them through Dr. Yanagisawa’s research group. On the basis of these results, the compounds will be re-designed and optimized to lead to the candidates for preclinical trial. For attaining the above work, we have to study not only organic chemistry but medical and pharmaceutical sciences, biochemistry, molecular biology, pharmacology, ADME study and drug formulation. If you join our group, you could study these fields through direct on-the-job training.

Lead Optimization

We are also studying opioid compounds (morphine-like compounds) which bind to the opioid receptor to afford mainly analgesic properties, but also addiction. Although many researchers had been trying to isolate the addiction from opioids, the trials were in vain. Recently, the opioid receptor was divided to three classes (μ, δ, κ) and the addiction was clarified to be attributed to the μ receptor type. Since the finding, many researchers in the world have been trying to design and synthesize κ agonists for obtaining ideal opioids without addictive properties.

Only our group could release the first κ receptor agonist in the world, nalfurafine (indication: antipruritic for kidney dialysis patients, commercial name: Remitch® Capsules) by use of rational drug design (accessory site theory from κ antagonist, nor-BNI).

Opioids are expected to be ideal drugs for many diseases, not only for severe pain, but pollakiuria, depression, anxiety and adiposity. Furthermore, as opioids were reported to interact with the orexin receptor, we would like to aim for obtaining drugs which participate with both opioid and orexin receptors.

Application Of Technology for QOL

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Related Sites

  • IIIS
  • WPI


IIIS Building 4F, University of Tsukuba

1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 TEL/FAX +81-29-853-6568


We are engaged in the design and synthesis of orexin receptor agonists, and also opioid research in WPI-IIIS, University of Tsukuba.