Chemical Biology on Regulation of Gene Transcription by Small Molecules

2009 Fiscal Year Self-evaluation Report

• Project/Area Number: 19201044
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Living organism molecular science
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: KAGECHIKA Hiroyuki Tokyo Medical and Dental University, 大学院・疾患生命科学研究部, 教授 (20177348)
• Project Period (FY): 2007 – 2010

Research Abstract

本研究では、低分子化合物により活性化されることによって特異的な応答遺伝子の発現を制御する種々の核内受容体の作用制御物質を創製することを目的とする。当面の標的とする核内受容体はレチノイド(RARとRXR)、ビタミンD(VDR)、甲状腺ホルモン(TR)、脂質・糖質・コレステロール代謝等での重要な働きをする核内受容体PPAR、LXR、FXR、そしてリガンド未知のオーファン受容体群である。具体的な研究計画は主に以下の6項目からなる。
(1)オーファン核内受容体の内因性および合成リガンドの探索
(2)ヘテロダイマーパートナー選択的なレチノイド受容体RXRリガンドの創製
(3)リガンド依存的な核内受容体と種々の転写因子との相互作用解析
(4)受容体変異解析法によるリガンド依存性の解析
(5)核内受容体機能解析のためのバイオプローブの開発と応用
(6)疎水性ファーマコフォアとしてのホウ素クラスター研究

Research Products

• [Journal Article] Activation of Testicular Orphan Receptor 4 by Fatty Acids (2009)
  • Author(s): Tsai, N.-P., Huq, M., Gupta, P., Yamamoto, K., Kagechika, H., Wei, L.-N.
  • Journal Title: Biochim.Biophys.Acta-Gene Regul.Mech. 1789 Pages: 734-740
• [Journal Article] Contribution of AP-1 interference induced by TAC-101 to tumor growth suppression in a hepatocellular carcinoma model (2009)
  • Author(s): Eshima, K., Fukaya S., Sugimoto, A., Mori, T., Yokoi, H., Yamamoto, Y., Sugiura, S., Honda, S., Masuko, N., Murakami, K., Yamasaki, Y., Kagechika, H.
  • Journal Title: Tumor Biol. 30 Pages: 1-7
• [Journal Article] Fluorescent visualization of the conformational change of aromatic amide or urea induced by N-methylation (2009)
  • Author(s): Hirano, T., Osaki, T., Fujii, S., Komatsu, D., Azumaya, I., Tanatani, A., Kagachika, H.
  • Journal Title: Tetrahedron Lett 50 Pages: 488-491
• [Journal Article] Acidic heterocycles as novel hydrophilic pharmacophore of androgen receptor ligands with a carborane core structure (2009)
  • Author(s): Fujii, S., Ohta, K., Goto, T., Kagechika, H., Endo, Y.
  • Journal Title: Bioorg.Med.Chem. 17 Pages: 344-350
• [Journal Article] The RXR agonists PA024 and HX630 have different abilities to activate LXR/RXR and to induce ABCA1 expression in macrophage cell line (2008)
  • Author(s): Nishimaki-Mogami, T., Tamehiro, N., Sato, Y., Okuhira, K., Sai, K., Kagechika, H., Shudo, K., Abe-Dohmae, S., Yokoyama, S., Ohno, Y., Inoue, K., Sawada, J.
  • Journal Title: Biochem.Pharmacol. 76 Pages: 1006-1013
• [Presentation] Development of Novel Synthetic Ligands for Nuclear Receptors (2010)
  • Author(s): Kagechika, H.
  • Organizer: The 14^<th> International Congress of Endocrinology (ICE2010)
  • Place of Presentation: 京都
  • Year and Date: 2010-03-30
• [Presentation] ビタミンA 新しい構造、機能、そして医薬へ (2009)
  • Author(s): 影近弘之
  • Organizer: 第326回脂溶性ビタミン総合研究委員会
  • Place of Presentation: 静岡
  • Year and Date: 2009-12-04
• [Presentation] Development of Novel Non-secosteroidal Vitamin D Receptor Ligands Based on Carborane as A Hydrophobic Core Structure (2009)
  • Author(s): Fujii, A., Kano, A., Sekine, R., Kawachi, E., Masuno, H., Hirano, T., Tanatani, A., Kagechika, H.
  • Organizer: 14^<th> Vitamin D Workshop
  • Place of Presentation: Brugge, Belgium
  • Year and Date: 2009-10-04
• [Presentation] レチノイド : 活性ビタミンAの医薬展開 (2008)
  • Author(s): 影近弘之
  • Organizer: 第386回国際治療談話会例会
  • Place of Presentation: 東京
  • Year and Date: 2008-09-18
• [Presentation] Novel synthetic RAR- and RXR-selective agonists bearing a unique structure in the hydrophobic part (2008)
  • Author(s): Kagechika, H., Muratake, H., Amano, Y., Noguchi, M., Shudo. K.
  • Organizer: FASEB meeting on Retinoid
  • Year and Date: 2008-06-15
• [Book] Expert Opinion(Thyromimetics : a review of recent reports and patents (2004-2009)) (2010)
  • Author(s): Hirano, T., Kagechika, H.
  • Total Pages: 213-228
• [Book] Combinatorial methodologies for development of chemical and biological sensors(Ed. by Potyrailo, R. A. ; Mirsky, V. M., Construction of Coumarin Library for Development of Fluorescent Sensors, Chapter 18) (2009)
  • Author(s): Hirano, T., Kagechika, H.
  • Total Pages: 441-451
  • Publisher: Springer
• [Book] Gene Family Based Molecular Design(Edited by Karen Lackey., Nuclear Receptor Drug Discovery, Chapter 9) (2008)
  • Author(s): Kagechika, H., Tanatani, A.
  • Total Pages: 275-316
  • Publisher: Wiley-Interscience
• [Patent(Industrial Property Rights)] PRアンタゴニスト活性を有するクマリン誘導体 (2010)
  • Inventor(s): 棚谷綾, 酒井悠, 影近弘之, 平野智也
  • Industrial Property Rights Holder: お茶の水女子大学、東京医科歯科大学
  • Industrial Property Number: 特願2010-43034
  • Filing Date: 2010-02-26
• [Patent(Industrial Property Rights)] レチノイドXレセプター機能調節剤 (2009)
  • Inventor(s): 影近弘之
  • Industrial Property Rights Holder: 東京医科歯科大学
  • Industrial Property Number: 特願2009-4977
  • Filing Date: 2009-03-03