| Project/Area Number |
15K18830
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Chemical pharmacy
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| Research Institution | The University of Tokushima |
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Principal Investigator |
NAKAYAMA Atsushi 徳島大学, 大学院医歯薬学研究部(薬学系), 助教 (60743408)
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 天然マクロライド / 多発性骨髄腫 / マクロライド / 全合成 / 骨髄腫 |
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| Outline of Final Research Achievements |
LL-Z1640-2 (1) is a member of 14-membered macrolide containing cis-enone moiety . This is known as a potent and selective TAK-1 (TGF-b activated kinase 1) inhibitor. Recently, we revealed that 1 exhibited a marked tumor reduction effect for multiple myeloma(MM)-bearing mice. Moreover the osteolytic bone destruction which is caused in MM was also suppressed by the administration of LL-Z1640-2. Although LL-Z1640-2 can be considered as a promising seed molecule of antitumor drug, the supplement of it is not stable for the further animal experiments. To facilitate the development of anti-MM agent, the establishment of the novel synthetic route of LL-Z1640-2 was conducted. This synthesis involved a ring-closing metathesis under low temperature as a key reaction and last stage isomerization from cis-enone to trans-enone. As a result, four derivatives including LL-Z1640-2 were obtained throughout this total synthesis and we also discovered some derivatives which have potent anti-MM agents.
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