Screening of inhibitors of bone morphogenetic protein (BMP) signaling on Fibrodysplasia ossificans progressiva (FOP) from natural resources

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K15134
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Natural medicines
• Research Institution: Tohoku Medical and Pharmaceutical University (2017-2018); Kitasato University (2016)
• Principal Investigator: UCHIDA Ryuji 東北医科薬科大学, 薬学部, 教授 (60280632)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 進行性異所性骨化線維異形性症 (FOP) / BMPシグナル伝達 / 阻害剤 / 天然資源

Outline of Final Research Achievements

Fibrodysplasia ossificans progressiva (FOP) is a rare congenital disorder of progressive and widespread postnatal heterotopic bone formation in soft tissues. Accordingly, we have screened microbial metabolites for inhibitors of bone morphogenetic protein (BMP) signaling on two types of cell-based assay system with a pathological mutation of FOP. As a result, three novel compounds, designated scopranones, were isolated from the culture broth of Streptomyces sp. BYK-11038. Scopranones have an unusual common structure with two atypical scooplike moieties linked at the tails to form part of a unique 3-furanone ring. In addition, destruxins and citreoviridins were isolated from fungal cultures broths, and lamellolactones and dyssidenins were isolated from sponges.

Free Research Field

天然物化学

Academic Significance and Societal Importance of the Research Achievements

今回新規化合物として見出したscopranoneは、その新規な構造から有機化学の研究者によって全合成が達成され、構造活性相関研究が進められている。また、生合成研究にも興味が持たれ、遺伝子レベルでの解析も行われていることから、他の研究領域にも注目される化合物を提供できている。さらに、治療法が全く確立されていない難病FOPの予防治療薬の開拓を目的とした本研究は、社会的貢献度の高い内容と考えられる。