Discovery of inhibitors for nuclear receptor functions with multiple mechanisms
| Project/Area Number |
21790108
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Drug development chemistry
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| Research Institution | The University of Tokyo |
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Principal Investigator |
ISHIKAWA Minoru The University of Tokyo, 分子細胞生物学研究所, 助教 (70526839)
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| Project Period (FY) |
2009 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2009: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | 核内受容体 / リガンド / コアクチベーター阻害 / 核内受受容体 / 非ステロイドリガンド / 拮抗物質 / ビタミンD受容体 / ペプチド等価体 / 構造展開 / 転写抑制 |
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| Research Abstract |
Nuclear receptors (NRs) are ligand-dependent transcription factors which regulate the expression of responsive genes and thereby affect diverse diseases. Once an agonist activates the NR, recruitment of additional coactivator proteins is essential for transcription. NRs modulators often possess issues, including cross reactivity with other NRs, and existence of drug-resistant cancers. To overcome these issues, I aimed multiple inhibitions of NRs functions. First, five kinds of NRs modulators with different skeletons from physiological ligands were generated. Second, non-peptide coactivator mimetics for a NR were generated. Now, hybrid molecules consisting of modulators for NRs linked to coactivator mimetics are being prepared. On the other hand, we developed a method that induces selective degradation of target proteins by small molecules (protein knockdown). Utilizing this method, a compound that inhibits a NR function with multiple mechanisms (antagonism and decrease of the NR) was generated.
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Report
(3 results)
Research Products
(43 results)
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[Journal Article] LXXLL peptide mimetics as inhibitors of the interaction of vitamin Dreceptor with coactivators2010
Author(s)
Mita, Y., Dodo, K., Noguchi-Yachide, T, Miyachi, M., Makishima, M., Hashimoto, Y., Ishikawa, M.
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Journal Title
Bioorganic & Medicinal Chemistry Letters 20
Pages: 1712-1717
Related Report
Peer Reviewed
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