Chemical biological approach for regulation of gene expression

2010 Fiscal Year Final Research 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 東京医科歯科大学, 大学院・疾患生命科学研究部, 教授 (20177348)
• Co-Investigator(Kenkyū-buntansha): HIRANO Tomoya 東京医科歯科大学, 生体材料工学研究所, 准教授 (20396980) ; YAMAMOTO Keiko 昭和薬科大学, 薬学部, 教授 (90147017) ; SHUDO Koichi (財)乙卯研究所, 所長 (50012612)
• Project Period (FY): 2007 – 2010
• Keywords: 遺伝子転写制御 / 核内受容体 / ケミカルバイオロジー / レチノイド / ビタミンD / アンドロゲン / プロゲステロン / 蛍光性リガンド

Research Abstract

Nuclear receptors are ligand-inducible transcription factors that regulate the expression of their target genes. Nuclear receptors have become one of the most significant molecular targets for drug discovery in the fields of cancer, metabolic syndrome, autoimmune diseases, and so on. We have developed various nuclear receptors ligands useful for regulation of each nuclear receptor or for elucidation of the functions.

Research Products

• [Journal Article] Retinoid X receptorgamma signaling accelerates CNSremyelination (2011)
  • Author(s): Huang, J. K.; Jarjour, A. A.; Nait-Oumesmar, B.; Kerninon, C.; Williams, A. Krezel, W.; Kagechika, H.; Bauer, J.; Zhao, C.; Baron-Van Evercooren, A.; Chambon, P.; ffrench-Constant, C.; Franklin, R. J. M.
  • Journal Title: Nature Neurosci Volume: 14 Pages: 45-53
  • Peer Reviewed
• [Journal Article] Tributyltin chlorideinduces ABCA1 expression andapolipoprotein A-I-mediated cellularcholesterol efflux by activatingLXRalpha/RXR (2011)
  • Author(s): Cui, H.; Okuhira, K.; Ohoka, N.; Naito, M.; Kagechika, H.; Hirose, A, ; Nishimaki-Mogami, T.
  • Journal Title: Biochem. Pharmacol Volume: 81 Pages: 819-824
  • Peer Reviewed
• [Journal Article] Modulation of intramolecularheterodimer-induced fluorescencequenching of tricarbocyanine dye for thedevelopment of fluorescent sensors (2010)
  • Author(s): Hirano, T.; Akiyama, J.; Mori, S.; Kagechika, H.
  • Journal Title: Org. Biomol. Chem Volume: 8 Pages: 5568-5575
  • Peer Reviewed
• [Journal Article] Design and Synthesis ofNovel Retinoid Synergists having aDibenzodiazepine Skeleton (2010)
  • Author(s): Ohta, K.; Kawachi, E.; Shudo, K.; Kagechika, H.
  • Journal Title: Heterocycles Volume: 81 Pages: 2465-2470
  • Peer Reviewed
• [Journal Article] Developmentof novel bisubstrate-type inhibitors ofhistone methyltransferase SET7/9 (2010)
  • Author(s): Mori, S.; Iwase, K.; Iwanami, N.; Tanaka, Y.; Kagechika, H.; Hirano, T.
  • Journal Title: Bioorg. Med. Chem Volume: 18 Pages: 8158-8168
  • Peer Reviewed
• [Journal Article] Efficient Induction of CCR9 onT Cells Requires Coactivation of RetinoicAcid Receptors and Retinoid X Receptors (RXRs): Exaggerated T Cell Homing to theIntestine by RXR Activation withOrganotins (2010)
  • Author(s): Takeuchi, H.; Yokota, A.; Ohoka, Y.; Kagechika, H.; kato, C.; Song, S.-Y.; Iwata, M.
  • Journal Title: J. Immunol Volume: 185 Pages: 5289-5299
  • Peer Reviewed
• [Journal Article] Retinoic Acid Induces Expression of theThyroid Hormone Transporter, Monocarboxylate Transporter 8(Mct8) (2010)
  • Author(s): Kogai, T.; Liu, Y.-Y.; Richter, L. L.; Mody, K.; Kagechika, H.; Bent, G. A.
  • Journal Title: J. Biol. Chem Volume: 285 Pages: 27279-27288
  • Peer Reviewed
• [Journal Article] Inhibition of Mammary Carcinoma CellGrowth by RXR is Mediated by the Receptor's Oligomeric Switch (2010)
  • Author(s): Yasmin, R.; Kannan-Thulasiraman, P.; Kagechika, H.; Dawson, M. I.; Noy, N.
  • Journal Title: J. Mol. Biol. Volume: 397 Pages: 1121-1131
  • Peer Reviewed
• [Journal Article] Activation of Testicular Orphan Receptor4 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 Volume: 1789 Pages: 734-740
  • Peer Reviewed
• [Journal Article] Encapsulation of thesynthetic retinoids Am80 and LE540 intopolymeric micelles and the retinoids' rerease control (2009)
  • Author(s): Satoh, T.; Higuchi, Y.; Kawakami, S.; Hashida, M.; Kagechika, H.; Shudo, K.; Yokoyama, M.
  • Journal Title: J. Controlled Release Volume: 136 Pages: 187-195
  • Peer Reviewed
• [Journal Article] Activation of the PI3 Kinase Pathway By Retinoic Acid Mediates Sodium/Iodide Symporter Induction and Iodide Transport in MCF-7 Breast CancerCells (2009)
  • Author(s): Ohashi, E.; Kogai, T.; Kagechika, H.; Brent, G. A.
  • Journal Title: Cancer Res Volume: 69 Pages: 3443-3450
  • Peer Reviewed
• [Journal Article] Thetranscriotion factors Nur77 and retinoid X receptors participate in amphetamine-induced locomotor activities (2009)
  • Author(s): Bourhis, E.; Maheux, J.; Paquet, B.; Kagechika, H.; Shudo, K.; Rompre, P.; Rouillard, C.; Levesque, D.
  • Journal Title: Psychopharmacol Volume: 202 Pages: 635-648
  • Peer Reviewed
• [Journal Article] ApoC-III gene expression issharply increased during adipogenesis andis augmented by retinoid X receptor(RXR) agonists (2009)
  • Author(s): Takahashi, Y.; Inoue, J.; Kagechika, H.; Sato, R.
  • Journal Title: FEBS Lett Volume: 583 Pages: 493-497
  • Peer Reviewed
• [Journal Article] Contribution of AP-1 interference induced by TAC-101 totumor growth suppression in ahepatocellular 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: TumorBiol Volume: 30 Pages: 1-7
  • Peer Reviewed
• [Journal Article] Acidicheterocycles as novel hydrophilicpharmacophore of androgen receptorligands with a carborane core structure. Bioorg (2009)
  • Author(s): Fujii, S.; Ohta, K.; Goto, T.; Kagechika, H.; Endo, Y.
  • Journal Title: Med. Chem Volume: 17 Pages: 344-350
  • Peer Reviewed
• [Journal Article] Effects of retinoic acids on the dendritic morphology of cultured hippocampal meurons (2008)
  • Author(s): Liu, Y.; Kagechika, H.; Ishikawa, J.; Hirano, H.; Matsukuma, S.; Tanaka, K.; Nakamura, S.
  • Journal Title: J. Neurochem Volume: 106 Pages: 1104-1116
  • Peer Reviewed
• [Journal Article] The RXRagonists PA024 and HX630 have different abilities to activate LXR/RXR and toinduce ABCA1 expression in macrophage cellline (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 Volume: 76 Pages: 1006-1013
  • Peer Reviewed
• [Journal Article] Identification of An Intermediate in the Deboronation of or tho-Carborane : An Adduct of ortho-Carborane with Two Nucleophiles on One Boron Atom (2008)
  • Author(s): Taoda, Y.; Sawabe, T.; Endo, Y. Yamaguchi, K.; Fujii, S.; Kagechika, H.
  • Journal Title: Chem. Commun Pages: 2049-2051
  • Peer Reviewed
• [Journal Article] b-Cryptoxanthin, a novel natural RAR ligand, induces ATP-binding cassette transporters inmacrophages (2007)
  • Author(s): Matsumoto, A.; Mizukami, H.; Mizuno, S.; Umegaki, K.; Nishikawa, J.; Shudo, K.; Kagechika, H.; Inoue, M.
  • Journal Title: Biochem. Pharmacol Volume: 74 Pages: 256-264
  • Peer Reviewed
• [Journal Article] STAT5a/PPARg Pathway Regulates Involucrin Expression in Keratinocyte Differentiation (2007)
  • Author(s): Dai, X.; Sayama, K.; Shirakata, Y.; Hanakawa, Y.; Yamasaki, K.; Tokumaru, S.; Yang, L.; Wang, X.; Hirakawa, S.; Tohyama, M.; Yamauchi, T.; Kadowaki, T.; Kagechika, H.; Hashimoto, K.
  • Journal Title: J. Invest. Dermatol Volume: 127 Pages: 1728-1735
  • Peer Reviewed
• [Presentation] ホウ素クラスターを疎水性骨格とする新規非セコステロイド型ビタミンD誘導体:受容体結合様式と構造展開 (2010)
  • Author(s): 藤井晋也,増野弘幸,垰田善之,加納敦,中林誠,伊藤暢聡,河内恵美子,清水正人,棚谷綾,平野智也,影近弘之
  • Organizer: 日本レチノイド研究会第21回学術集会
  • Place of Presentation: 高槻
  • Year and Date: 20101100
• [Presentation] クマリン骨格を基盤とした蛍光センサーの効率的開発法の構築と、蛍光性プロゲステロン受容体リガンド開発への応用 (2010)
  • Author(s): 平野智也,酒井悠,白石拓也,森修一,藤井晋也,棚谷綾,影近弘之
  • Organizer: 第4回バイオ関連化学シンポジウム
  • Place of Presentation: 大阪
  • Year and Date: 20100900
• [Presentation] Development of NovelAndrogen Antagonists Based on Hydrophobic Boron Clusters (2010)
  • Author(s): Fujii, S., Yamada, A., Ohta, K., Endo, Y., Kagechika, H.
  • Organizer: EFMC-ISMC2010 21^<st> International Symposium on MedicinalChemistry
  • Place of Presentation: Brussels, Bergium
  • Year and Date: 20100900
• [Presentation] カルボランを疎水性骨格とするビタミンD誘導体とその核内受容体結合様式 (2010)
  • Author(s): 影近弘之,藤井晋也,増野弘幸,平野智也,伊藤暢聡,伊倉貞吉,棚谷綾
  • Organizer: 第7回中性子捕獲療法学会
  • Place of Presentation: 東京
  • Year and Date: 20100800
• [Presentation] カルボランを疎水性骨格とする新規アンドロゲン受容体リガンドの創製 (2010)
  • Author(s): 藤井晋也,山田歩,太田公規,遠藤泰之,影近弘之
  • Organizer: 第7回中性子捕獲療法学会
  • Place of Presentation: 東京
  • Year and Date: 20100800
• [Presentation] VDR活性をもつLCA誘導体の合成とVDR結合構造の解析 (2010)
  • Author(s): 増野弘幸,数井優子,伊倉貞吉,中林誠,伊藤暢聡,藤井晋也,河内恵美子,棚谷綾,影近弘之
  • Organizer: ビタミン学会第62回大会
  • Place of Presentation: 岩手
  • Year and Date: 20100500
• [Presentation] 変異ARを有するLNCaP細胞に対して有効な新規ARアンタゴニストの創製 (2010)
  • Author(s): 山田歩,富田景子,長野麻央,藤井晋也,原山尚,太田公規,遠藤泰之,影近弘之
  • Organizer: ケミカルバイオロジー学会第5回年会
  • Place of Presentation: 東京
  • Year and Date: 20100500
• [Presentation] Development of Novel Synthetic Ligands for Nuclear Receptors (2010)
  • Author(s): Kagechika, H.
  • Organizer: The 14th International Congress ofEndocrinology(ICE2010)
  • Place of Presentation: Kyoto
  • Year and Date: 20100300
• [Presentation] Development of Novel Non-seco-Stroid-type Vitamin DDerivatives (2010)
  • Author(s): Kagechika, H.
  • Organizer: ICE2010 Official Satellite Symposium-Nuclear Receptor and its Frontier-
  • Place of Presentation: Kyoto
  • Year and Date: 20100300
• [Presentation] Development of Novel Nonsteroidal AndrogenReceptor Ligands Based on Hydrophobic BoronClusters (2010)
  • Author(s): Fujii, S., Ohta, K., Endo, Y., Kagechika, H.
  • Organizer: ICE2010 Official Satellite Symposium-Nuclear Receptor and its Frontier-
  • Place of Presentation: Kyoto
  • Year and Date: 20100300
• [Presentation] 核内受容体を分子標的とした医薬化学研究-レチノイドを中心に (2010)
  • Author(s): 影近弘之
  • Organizer: Metabolic Syndrome Seminar
  • Place of Presentation: 岡山
  • Year and Date: 20100200
• [Presentation] 変異ARに対して有効なカルボラン含有新規ARアンタゴニストの創製 (2009)
  • Author(s): 山田歩,富田景子,長野麻央,藤井晋也,原山尚,太田公規,遠藤泰之,影近弘之
  • Organizer: 第28回メディシナルケミストリーシンポジウム
  • Place of Presentation: 東京
  • Year and Date: 20091100
• [Presentation] カルボランを疎水性骨格とする新規非ステロイド型VDRリガンドの構造展開 (2009)
  • Author(s): 藤井晋也,加納敦,平野智也,河内恵美子,増野弘幸,棚谷綾,中林誠,伊倉貞吉,伊藤暢聡,清水正人,影近弘之
  • Organizer: 第35回反応と合成の進歩シンポジウム
  • Place of Presentation: 金沢
  • Year and Date: 20091100
• [Presentation] Development ofNovel Non-secosteroidal Vitamin DReceptor Ligands Based on Carborane as AHydrophobic Core Structure (2009)
  • Author(s): Fujii, S., Kano, A., Sekine, R., Kawachi, E., Masuno, H., Hirano, T., Tanatani, A., Kagechika, H.
  • Organizer: 14th Vitamin D Workshop
  • Place of Presentation: Brugge, Belgium
  • Year and Date: 20091000
• [Presentation] Crystal Structures of Non-secosteroidLigands Bound to Vitamin D NuclearReceptor (2009)
  • Author(s): Masuno, H., Fujii, S., Nakabayashi, M., Ikura, T., Ito, N., Shimizu, M., Kagechika, H.
  • Organizer: 14th Vitamin D Workshop
  • Place of Presentation: Brugge, Belgium
  • Year and Date: 20091000
• [Presentation] Tricarbocyanine系蛍光物質の会合現象制御による蛍光センサーの開発 (2009)
  • Author(s): 平野智也,秋山淳,影近弘之
  • Organizer: 第24回生体機能関連化学シンポジウム
  • Place of Presentation: 福岡
  • Year and Date: 20090900
• [Presentation] Development of a novel "functional" fluorescent labeling reagents for variousligand molecules (2009)
  • Author(s): Hirano, T., Akiyama, J., Kagechika, H.
  • Organizer: World Molecular ImagingCongress
  • Place of Presentation: Montreal, Canada
  • Year and Date: 20090900
• [Presentation] 新規非セコステロイド型VDRリガンドの構造展開と受容体結合様式の解析 (2009)
  • Author(s): 藤井晋也,加納敦,平野智也,河内恵美子,増野弘幸,棚谷綾,中林誠,伊倉貞吉,伊藤暢聡,清水正人,影近弘之
  • Organizer: ビタミン学会第61回大会
  • Place of Presentation: 亀岡
  • Year and Date: 20090500
• [Presentation] Novelnon-seco-steroidal VDR ligands bearing acarborane as a hydrophobic pharmacophore (2008)
  • Author(s): Kagechika H, Kano A, Fujii S, Hirano T, Kawachi E, Tanatani A
  • Organizer: XIII IMEBORON
  • Place of Presentation: Spain
  • Year and Date: 20080900
• [Presentation] Development of Novel Inhibitors of Histone Methyltransferase (2008)
  • Author(s): Hirano T, Hoshino K, Iwanami N, TanakaY, Kagechika H
  • Organizer: 236th ACS National Meeting
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 20080800
• [Presentation] Novel synthetic RAR and RXR-selective agonists bearing aunique structure in the hydrophobic part (2008)
  • Author(s): Kagechika H, Muratake H, Amano Y, Noguchi M, Shudo K
  • Organizer: FASEB meeting on Retinoid
  • Place of Presentation: New Haven, USA
  • Year and Date: 20080600
• [Book] Constructionof Coumarin Library for Development of Fluorescent Sensors, In' Combinatorialmethodologies for development of chemicaland biological sensors' Ed (2009)
  • Author(s): Hirano, T.; Kagechika, H.
  • Total Pages: 441-451
  • Publisher: Springer
• [Book] フォルダマー、In超分子サイエンス & テクノロジー基礎からイノベーションまで(国武豊喜監修)第3章、第1節 (2009)
  • Author(s): 影近弘之、棚谷綾
  • Total Pages: 467-476
  • Publisher: NTS
• [Book] NuclearReceptor Drug Discovery in Gene Family Based Molecular Design, Edited by KarenLackey (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、2009-049777
  • Filing Date: 2009-03-03