Development of sialidase inhibitors for treatment of idiopathic pulmonary fibrosis

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K19072
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 38:Agricultural chemistry and related fields
• Research Institution: Gifu University
• Principal Investigator: Imamura Akihiro 岐阜大学, 応用生物科学部, 准教授 (30610951)
• Project Period (FY): 2021-07-09 – 2023-03-31
• Keywords: 特発性肺線維症 / IPF / シアリダーゼ / NEU1 / シアル酸 / 有機合成

Outline of Final Research Achievements

This study aimed to develop a potent inhibitor of human sialidase NEU1 as a new therapeutic agent for human idiopathic pulmonary fibrosis (IPF), a nationally designated intractable disease. In our previous research, we found a lead compound capable of inhibiting NEU1 with high enzyme-selectivity and to a high degree. This study focused on creating compounds with higher inhibitory activity.
In this study, we designed four new compounds and chemically synthesized them. Though the NEU1 inhibitory activity of some compounds obtained showed activities equivalent to that of the lead compound, we could not get any compounds that surpassed the lead one. On the other hand, we successfully established a new synthetic route for the lead compound and realized large-scale synthesis.

Free Research Field

応用糖質化学

Academic Significance and Societal Importance of the Research Achievements

国指定難病である特発性肺線維症(IPF)の治療薬は限られており、有効性の高い新規治療薬の開発が強く望まれている。本研究では、従来の治療薬とは異なり、シアリダーゼNEU1の機能阻害を作用機序とする新規IPF治療薬の開発を目指した。本研究では、NEU1を酵素選択的かつ高度に阻害する化合物の大量合成法を確立するとともに、阻害活性に重要となる分子構造を見出した。今後、さらなる阻害活性の向上に向け、分子構造の精査および合成法の確立を行うことで、IPFに対する新規阻害薬の開発につながると期待できる。