| Project/Area Number |
16K19596
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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 |
Collagenous pathology/Allergology
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| Research Institution | University of Toyama |
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Principal Investigator |
OKAMOTO Naoki 富山大学, 大学院医学薬学研究部(医学), 研究員 (80727488)
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| Research Collaborator |
TAKI Hirofumi 富山大学, 大学院医学薬学研究部(医学), 准教授 (10240780)
ITO Tomoki 関西医科大学, 医学部, 准教授 (70434826)
OHTO Umeharu 東京大学, 大学院薬学系研究科, 准教授 (90451856)
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 全身性エリテマトーデス / 自然免疫 / TLR7 / 天然薬物 / 創薬 |
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| Outline of Final Research Achievements |
In this study, we evaluated the effectiveness of CB-7, a selective small molecule inhibitor of TLR7, aiming at developing therapeutic agents for systemic lupus erythematosus (SLE). CB-7 showed inhibitory activities against TLR7 in murine and human immune cells. However, the effectiveness of CB-7 in SLE model mice was not proven, and we found that CB-7 has problems in pharmacokinetics and metabolic stability. In order to solve these problems, CB-7 derivatives were synthesized. Several derivatives showed higher inhibitory activities than CB-7, and the structure-activity relationship on TLR7 inhibition was also revealed. We have already undertaken further synthesis of derivatives based on structural biology to optimize the biological activity. This will allow us to obtain a more potent TLR7 inhibitor with high metabolic stability.
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