Analysis of antiviral activity of 25-hydroxycholesterol

• Project/Area Number: 26860050
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: National Institute of Health Sciences
• Principal Investigator: Shibata Norihito 国立医薬品食品衛生研究所, 遺伝子医薬部, 主任研究官 (30391973)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 酸化コレステロール

Outline of Final Research Achievements

Although it is well known that many viruses can cause severe diseases, existing drugs against viruses are not sufficient and development of novel anti-virus drugs is required. Previously, I found that 25-hydroxycholesterol (25OHC) can inhibit virus replication without affecting on the viability of host cells. In this study, I investigated the molecular mechanism how 25OHC is recognized by the host cells, and how 25OHC induces the expression of specific stress-related genes. These results suggest that 25OHC may be a promising target for development of a novel anti-virus drug.

Research Products

• [Journal Article] Development of BCR-ABL degradation inducers via the conjugation of an imatinib derivative and a cIAP1 ligand. (2016)
  • Author(s): Demizu, Y., Shibata, N., Hattori, T., Ohoka, N., Motoi, H., Misawa, T., Shoda, T., Naito, M. & Kurihara, M.
  • Journal Title: Bioorg Med Chem Lett Volume: 26 Issue: 20 Pages: 4865-4869
  • DOI: 10.1016/j.bmcl.2016.09.041
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Induction of proteasomal degradation of ERα and subsequent cell death in breast cancer cells (2016)
  • Author(s): K. Okuhira, Y. Demizu, T. Hattori, N. Ohoka, N. Shibata, T. Nishimaki-Mogami, H. Okuda, M. Kurihara, M. Naito*
  • Journal Title: Methods Mol. Biol. Volume: 1366 Pages: 549-560
  • DOI: 10.1007/978-1-4939-3127-9_42
  • ISBN: 9781493931262, 9781493931279
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Protein Knockdown Technology: Application of Ubiquitin Ligase to Cancer Therapy. (2016)
  • Author(s): Ohoka N, Shibata N, Hattori T, Naito M.
  • Journal Title: Current Cancer Drug Targets Volume: 16 Issue: 2 Pages: 136-146
  • DOI: 10.2174/1568009616666151112122502
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Degradation of Stop Codon Read-through Mutant Proteins via the Ubiquitin-Proteasome System Causes Hereditary Disorders. (2015)
  • Author(s): Shibata N, Ohoka N, Sugaki Y, Onodera C, Inoue M, Sakuraba Y, Takakura D, Hashii N, Kawasaki N, Gondo Y, Naito M
  • Journal Title: J. Biol. Chem. Volume: 290 Issue: 47 Pages: 28428-28437
  • DOI: 10.1074/jbc.m115.670901
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] プロテインノックダウン法を利用したアンドロゲン受容体タンパク質分解誘導剤の開発 (2017)
  • Author(s): 柴田識人、永井克典、森田陽子、宇治川治、大岡伸通、服部隆行、今枝泰宏、奈良洋、長展生、内藤幹彦
  • Organizer: 日本薬学会第137年会
  • Place of Presentation: 仙台
  • Year and Date: 2017-03-24
• [Presentation] 発がん因子BCR-ABLを分解する低分子化合物の開発 (2016)
  • Author(s): 柴田識人、大岡伸通、服部隆行、内藤幹彦
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-06
• [Presentation] BCR-ABLの蛋白質分解誘導剤開発を指向したBCR-ABL結合化合物の探索 (2016)
  • Author(s): 柴田 識人、大岡 伸通、服部 隆行、橋井 則貴、斎藤 臣雄、近藤 恭光、石井 明子、長田 裕之、内藤 幹彦
  • Organizer: 日本薬学会
  • Place of Presentation: パシフィコ横浜（神奈川県）
  • Year and Date: 2016-03-26
• [Presentation] 終止コドンリードスルー変異による蛋白質のユビキチン-プロテアソーム依存的な分解はある種の遺伝性疾患の原因となりえる (2015)
  • Author(s): 柴田 識人、大岡 伸通、権藤 洋一 、内藤 幹彦
  • Organizer: 日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県）
  • Year and Date: 2015-10-08
• [Presentation] 終止コドンのリードスルー変異によるユビキチン-プロテアソーム系を介した蛋白質の不安定化 (2015)
  • Author(s): 柴田 識人、大岡 伸通、櫻庭 喜行、権藤 洋一 、内藤 幹彦
  • Organizer: 日本薬学会
  • Place of Presentation: デザイン・クリエイティブセンター神戸（兵庫県）
  • Year and Date: 2015-03-25 – 2015-03-28
• [Presentation] 終止コドンのリードスルー変異によるユビキチン-プロテアソーム系を介した蛋白質の不安定化 (2014)
  • Author(s): 柴田 識人、大岡 伸通、櫻庭 喜行、権藤 洋一 、内藤 幹彦
  • Organizer: Symposium for young ubiquitin researchers in Japan“New Era in the Ubiquitin Research”
  • Place of Presentation: 国際高等研究所（京都府）
  • Year and Date: 2014-11-10 – 2014-11-12
• [Presentation] 終止コドンのリードスルー変異によるユビキチン-プロテアソーム系を介した蛋白質の不安定化 (2014)
  • Author(s): 柴田 識人、大岡 伸通、権藤 洋一 、内藤 幹彦
  • Organizer: 日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県）
  • Year and Date: 2014-09-25 – 2014-09-27