Integrated drug discovery study for conquering Alzheimer's disease

2014 Fiscal Year Final Research Report

• Project/Area Number: 23590137
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Drug development chemistry
• Research Institution: Kobe Pharmaceutical University (2014); Kobe Gakuin University (2011-2013)
• Principal Investigator: HAMADA Yoshio 神戸薬科大学, 薬学部, 研究員 (70424968)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Keywords: アルツハイマー病 / BACE1 / β-セクレターゼ / 酵素阻害剤 / ペプチド / アミロイドβ / 凝集阻害剤

Outline of Final Research Achievements

The increase of dementia patients is a big issue for Japan as it faces a rapidly aging society. To conquer Alzheimer’s disease, this research project aimed the development of BACE1 and Aβ aggregation inhibitors. Novel BACE1 inhibitors, YHI-309 and YHI-764 (IC50 = 13 nM and 26 nM, respectively), with a nitro or thiadiazole group were designed and synthesized. These compounds appear to have promise as drug candidates because of their increased membrane permeability.
Aβ aggregation inhibitors, YHI-008 and YHI-009, also designed and synthesized. These compounds exhibited potent inhibitory activity against the Aβ aggregation, and could recognize a specific Aβ conformer. These compounds are expected to use a research tool for pathogenic mechanism analysis.

Free Research Field

創薬化学