Development of small molecule that recruit AhR E3 ligase to target proteins.
| Project/Area Number |
16K08340
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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 |
Drug development chemistry
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| Research Institution | International University of Health and Welfare (2017-2019)
National Institute of Health Sciences (2016) |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | プロテインノックダウン / 芳香族炭化水素受容体 / プロテインノックダウン法 |
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| Outline of Final Research Achievements |
Targeted protein degradation using chimeric small molecules such as proteolysis-targeting chimeras (PROTACs) and specific and nongenetic inhibitors of apoptosis protein [IAP]-dependent protein erasers (SNIPERs) is an emerging modality in drug discovery. We expand the repertoire of E3 ligases capable of ubiquitylating target proteins using this system. By incorporating β-naphthoflavone (β-NF) as a ligand, we developed a novel class of chimeric molecules that recruit the arylhydrocarbon receptor (AhR) E3 ligase complex.
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| Academic Significance and Societal Importance of the Research Achievements |
細胞内の目的とするタンパク質をユビキチン－プロテアソーム系によって意図的に分解する方法がプロテインノックダウン法である。疾病の原因タンパク質を特異的に分解できれば新しい治療薬の開発が可能となる。今後、プロテインノックダウン法は新しい創薬の手法となるであろう。この研究では、ユビキチンリガーゼ活性を有する芳香族炭化水素受容体を利用したプロテインノックダウン法の開発を行った。ここで開発したプロテインノックダウン法分子は乳がんの新しい治療薬の開発につながると考えられる。
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Report
(5 results)
Research Products
(18 results)
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[Journal Article] Targeted Degradation of Proteins Localized in Subcellular Compartments by Hybrid Small Molecules.2017
Author(s)
Okuhira, K., Shoda, T., Omura, R., Ohoka, N., Hattori, T., Shibata, N., Demizu, Y., Sugihara, R., Ichino, A., Kawahara, H., Itoh, Y., Ishikawa, M., Hashimoto, Y., Kurihara, M., Itoh, S., Saito, H. & Naito, M.
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Journal Title
Mol pharmacol
Volume: 91
Issue: 3
Pages: 159-166
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[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.
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Journal Title
Bioorg Med Chem Lett
Volume: 26
Issue: 20
Pages: 4865-4869
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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