Development of orally active proteasome inhibitors using in vivo imaging.

2014 Fiscal Year Final Research Report

• Project/Area Number: 23510270
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Living organism molecular science
• Research Institution: Microbial Chemistry Research Foundation
• Principal Investigator: MOMOSE Isao 公益財団法人微生物化学研究会, 微生物化学研究所・沼津支所, 主席研究員 (10270547)
• Co-Investigator(Renkei-kenkyūsha): MASUDA Toru 公益財団法人微生物化学研究会, 微生物化学研究所沼津支所, 主席研究員 (90165720) ; WATANABE Takumi 公益財団法人微生物化学研究会, 微生物化学研究所, 主席研究員 (80270544) ; TATSUDA Daisuke 公益財団法人微生物化学研究会, 微生物化学研究所沼津支所, 研究員 (20442569) ; OHBA Shun-ichi 公益財団法人微生物化学研究会, 微生物化学研究所沼津支所, 研究員 (00601600) ; ABE Hikaru 公益財団法人微生物化学研究会, 微生物化学研究所, 研究員 (10462269)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Keywords: インビボイメージング / プロテアソーム / プロテアソーム阻害剤 / 経口剤

Outline of Final Research Achievements

Proteasome inhibitors were approved for treatment of multiple myeloma. Because these inhibitors are administered by intravenous bolus, new orally active proteasome inhibitors are desired. In this study, we developed a system for in vivo imaging of proteasome inhibition in the tumors of living mice, using a proteasome-sensitive fluorescent reporter. Then we used tyropeptin, which are produced by Kitasatospora sp. MK993-dF2, as a lead compound for the design of proteasome inhibitors, and synthesized tyropeptin derivatives. Finally, we found new orally active proteasome inhibitors using our in vivo imaging system and tyropeptin derivatives.

Free Research Field

天然物化学