Effects of IL-17 on intervertebral disc degeneration and the investigation of the new small-molecule IL-17 inhibitor for treating degenerative discs
| Project/Area Number |
17K10946
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Tokai University |
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Principal Investigator |
SUYAMA Kaori 東海大学, 医学部, 准教授 (20433914)
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| Co-Investigator(Kenkyū-buntansha) |
酒井 大輔 東海大学, 医学部, 准教授 (10408007)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | インターロイキン17 / 低分子化合物 / インシリコ創薬 / 椎間板 / IL-17 / 椎間板変性 / 創薬 |
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| Outline of Final Research Achievements |
IL-17A is a member of the IL-17 cytokine family, which mediates the induction of some inflammatory cytokines and chemokines. We evaluated the effects of IL-17A on nucleus pulposus (NP) cells and pharmacotherapeutic potential of the new small-molecule inhibitors that blockIL-17A receptor binding.
We analyzed the spatial structure of the protein-protein interactions between IL-17A and IL-17A receptor (IL-17RA), and identified four small-molecule inhibitors that accessed the IL-17A-binding site of IL-17RA, as determined by in silico analysis of numerous drug molecules. Our results showed that IL-17A promoted the expression of the factors which lead degeneration of intervertebral discs (IVD); however, the four small-molecule inhibitors suppressed augmentation of IVD degeneration factors. These results showed that IL-17A regulated the factors which mediate disc degeneration and the small-molecule inhibitor of IL-17A could be useful for pharmacotherapy of intervertebral disc disease.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は椎間板におけるIL-17Aの作用解析から薬物を使用した治療標的としての可能性までを包括した体系的研究である。既存のIL-17阻害剤は生物学的製剤が主体であり、副作用として重篤な感染症や高い薬価、投与法が注射薬に限定される点、等が問題とされている。これに対し低分子化合物の利点としては、生物学的製剤より安価であり、水溶性に優れるため外用薬、経口薬としての投与が可能となる等が挙げられる。現在、椎間板変性以外にも多くの疾患に対してIL-17Aの関与が報告されており、上述した低分子阻害剤化合物の利点はこれらの椎間板疾患を含めたIL-17関連疾患に対する新しい治療薬としての応用も期待できる。
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Report
(4 results)
Research Products
(11 results)
