ホーム > 認知症先進医療開発センター > English Pages > Department & Laboratories > Department of Drug Discovery

Department of Drug Discovery

Welcome to the website of Department of Drug Discovery.

Our purpose is to identify and develop the pre-emptive treatment for Alzheimer disease (AD) in collaboration with other academia (univ. and institution) and pharmaceutical companies.​  We will be developing innovative drugs for AD by making full use of the characteristics of the Center for Development of Advanced Medicine for Dimentia (CAMD), where specializes only in research and development for AD.

moe dock

Home

What's new?

  • Ms. AKTAR joined our team. (Dec., 2017)
  • We are recruiting colleague (1 post doc. or 1 technician) to work together with us. (Sept., 2017)
  • Dr. Imamura joined our team.  (Jul., 2017)
  • New patent was filed.  (Mar., 2017)
  • ​ASIM (Anti-seed internal medicine) was selected as a project that gets a boost by AMED (Japan Agency for Medical Research and Development).  (Jun., 2016)
  • Mr. Koyama and Ms. Yamagishi joined our team.  (Apr., 2016)
  • New patent was filed.  (Mar., 2016)

Back to the top

Department

Academic Drug Discovery

 CAMD focuses on the deep and extensive biology based on the understanding of AD pathophysiology.   In order to maximize the result from the basic research,  we layed out the unique framework of academic drug discovery through a close communication with basic science researchers. 

 Our purpose is to identify the clinical candidates acquired in vitro and in vivo Proof of Concept (POC) through target validation, establishment of screening cascade, hit identification by HTS, hit and lead optimization, pharmacological evaluation in disease animal model, and identification of surrogate biomarker.  We are keen to deliver the innovative drug to the patients. 

drug discovery

Staff

Department Head of Drug Discovery

Akiyoshi Kawai, Ph.D.
​Working experience in both Japanese and US Pharmas.

Sayaka Nishimura

Section of Drug Screening

Section Chief  vacant

SHARMIN AKTAR, Ph.D.
Mayumi Yamagishi

Section of Medicinal Chemistry

Section Chief 
Shinichi Imamura, Ph.D.

Koichi Takahashi, Ph.D.
Mami Ozako
Hiroshi Koyama

 

Instruments

bio instruments

medchem instrument

Laboratory

lab

Back to the top

Research topic

Section of Drug Screening

HTS

Section of Medicinal Chemistry

medchem

Project

1. ASIM (Anti-Seed Internal Medicine)

Our objective is to develop the pre-emptive treatment for Alzheimer disease (AD).  It is well-known that amyloid fibrils start accumulating in the brain during ten or twenty years before the clinical onset of AD.

amyloid cascade

  We previously examined autopsied brains including AD brains and discovered a unique Aβ species, which was characterized by its tight binding to GM1 ganglioside, specifically in the membrane fractions prepared from human brains in the early stage of AD.  On the basis of the molecular characteristics of the ganglioside-bound Aβ (GAβ), we hypothesized that Ab adopts an altered conformation (i.e. α-helix rich) through its binding to GM1, and then initiates Aβ assembly into fibrils (i.e. β-helix rich) by acting as an endogenous seed in the brain.  To date, this hypothesis has been strongly supported by various scientific evidence from multiple research groups.

To apply our findings of GAβ to the development of Anti-Seed Internal Medicine (ASIM) for AD, we have performed molecular dynamics analysis of the interaction between Aβ and the sugar chain of GM1.  Virtual screening against drug-like libraries based on the most stable GAβ model followed by the wet screening generated several promising hit compounds.  Hit optimization led to the identification of the lead compounds with markedly improved PK profiles.  The lead optimization is currently on-going, and several advanced leads have been identified.

Gaβ hypothesis

​​​

2. New project

We just commenced establishing the screening system for finding the hit compounds against the tau-induced toxicity.  Simultaneously, we are seeking a possibility of the next targets identified by the basic AD researechers not only in NCGG but also in other academia.

Back to the top

Message board

Recruit

Job still open

  • 1 post doc. in Biochemistry with experience in HTS 
  • 1 technician with experience in HTS

​If you are interested in the position, please feel free to contact us directly.

Contact info: Akiyoshi Kawai   E-mail: akawai(at)ncgg.go.jp

Back to the top

Impact

Patent filing

  • Katsuhiko Yanagisawa, Akiyoshi Kawai, Japanese Patent Application filed on March 29, 2017 for "Novel Quinoline Carboxylic Acid derivatives and their use as inhibitors of Aβ aggregation".
  • Katsuhiko Yanagisawa, Akiyoshi Kawai, PCT/JP216059576 filed on March 25, 2016.
  • Katsuhiko Yanagisawa, Akiyoshi Kawai, Japanese Patent Application No.2016-060199 filed on March 24, 2016 for "Novel Indole derivatives and their use as inhibitors of Aβ aggregation".
  • Katsuhiko Yanagisawa, Akiyoshi Kawai,Japanese Patent Application No.2015-062815 filed on March 25, 2015 for "Novel Oxadiazole derivatives and their use as inhibitors of Aβ aggregation".
  • Katsuhiko Yanagisawa, Akiyoshi Kawai, et al., Japanese Patent Application No.2014-140625 filed on July 8, 2014 for "Novel Benzoxazine derivatives and their use as inhibitors of Aβ aggregation.

Conference presentation

  • Kawai A, Yanagisawa K, Takahashi K, Hiramoto T, Kawanishi M, The international Chemical Congress of Pacific Basin Societies 2015, December 15, 2015, Honolulu (USA).

Back to the top

Access

http://www.ncgg.go.jp/camd/english/access.htmlこのリンクは別ウィンドウで開きます
Contact Info: Akiyoshi Kawai, Ph.D.
tel: +81-562-44-5651 (ext. 6502), +81-562-87-1278
E-mail: akawai(at)ncgg.go.jp

Back to the top

NCGG

  • National Center for Geriatrics and Gerontology
  • National Hospital for Geriatric Medicine, NCGG
  • Research Institute, NCGG
  • Center for Gerontology and Social Science

National Center for Geriatrics and Gerontology

7-430 Morioka-cho, Obu City, Aichi Prefecture, Japan