KAKEN — Research Projects | Researcher Number: 70114402

1. Elucidation of the mechanism of hepatitis B virus entry and control of infection by entry inhibitors

Research Project

Research Category	Grant-in-Aid for Scientific Research (B)
Review Section	Basic Section 53010:Gastroenterology-related
Research Institution	Aichi Medical University
Principal Investigator	伊藤清顕愛知医科大学, 医学部, 教授
Project Period (FY)	2022-04-01 – 2025-03-31Granted
Keywords	B型肝炎ウイルス / 侵入機構 / 侵入阻害 / 感染制御 / ウイルス侵入機構 / 胆汁酸誘導体 / 侵入阻害剤
Outline of Research at the Start	我々は、胆汁酸誘導体の一つであるINT-767がHBVのエンベロープ蛋白質の疎水性領域に結合してHBVの感染を強力に阻害することを発見した（Ito K et al. Hepatology. 2021）。本研究によりHBVの肝細胞内への侵入機構を分子レベルで解明し、胆汁酸誘導体や低分子化合物を利用して ...
Outline of Annual Research Achievements	B型肝炎ウイルス（HBV）はpreS1領域のN末端側やC末端側の疎水性領域を利用してNTCPとの結合やエンドソーム膜と膜融合して巧みに細胞内に侵入している。我々は、この侵入機構に対して、胆汁酸の一般的な性質である疎水面と親水面を持つ両親媒性物質としての界面活性作用と側鎖の電荷を利用して効果的に阻害す ...
Current Status of Research Progress	2: Research has progressed on the whole more than it was originally planned.

Research Products of this project	Journal Article (9 results, of which Int'l Joint Research: 2 results, Peer Reviewed: 8 results, Open Access: 5 results) Presentation (21 results, of which Int'l Joint Research: 3 results) Patent(Industrial Property Rights) (1 results, of which Overseas: 1 results)

2. Screening of cancer cell 3D invasion inhibitors from microbial metabolites

Research Project

Research Category	Grant-in-Aid for Scientific Research (C)
Research Field	Chemical biology
Research Institution	Aichi Medical University
Principal Investigator	Umezawa Kazuo 愛知医科大学, 医学部, 教授
Project Period (FY)	2017-04-01 – 2020-03-31Completed
Keywords	がん細胞 / 三次元培養 / 遊走 / 浸潤 / NF-kappa B / I-kappa B kinase / ketomycin / DHMEQ / 転移 / 放線菌 / スクリーニング / IKK-beta / 生理活性物質 / 微生物 / 阻害剤
Outline of Final Research Achievements	In the present research, we have screened low molecular weight compounds that inhibit cancer cell migration from microbial culture filtrates and our o ...

Research Products of this project	Int'l Joint Research (12 results) Journal Article (33 results, of which Int'l Joint Research: 13 results, Peer Reviewed: 32 results, Open Access: 1 results) Presentation (22 results, of which Int'l Joint Research: 5 results, Invited: 3 results) Remarks (6 results) Patent(Industrial Property Rights) (2 results)

3. Screening of NF-kappa B inhibitors having new core structure and application to aggressive cancer treatment

Research Project

Research Category	Grant-in-Aid for Scientific Research (C)
Research Field	Chemical biology
Research Institution	Aichi Medical University
Principal Investigator	Umezawa Kazuo 愛知医科大学, 医学部, 教授
Project Period (FY)	2014-04-01 – 2017-03-31Completed
Keywords	NF-kappa B / 分子デザイン / 天然物 / がん / 転移 / 炎症 / DHMEQ / desmal / 阻害剤 / スクリーニング / 分子標的 / SEMBL / 放線菌 / (-)-DHMEQ / Exo-ene EQ
Outline of Final Research Achievements	Metastasis inhibitors are expected as new chemotherapeutic agents with little side effects. We previously discovered DHMEQ as an NF-kappa B inhibitor. ...

Research Products of this project	Int'l Joint Research (8 results) Journal Article (45 results, of which Int'l Joint Research: 14 results, Peer Reviewed: 44 results, Acknowledgement Compliant: 8 results, Open Access: 11 results) Presentation (27 results, of which Int'l Joint Research: 5 results, Invited: 7 results) Remarks (6 results)

4. Development of novel drug for bone-related diseases using Pirin inhibitors

Research Project

Research Category	Grant-in-Aid for Scientific Research (B)
Research Field	Chemical biology
Research Institution	Keio University
Principal Investigator	SIMIZU Siro 慶應義塾大学, 理工学部, 准教授
Project Period (FY)	2012-04-01 – 2015-03-31Completed
Keywords	骨関連疾患 / Pirin / 破骨細胞 / 破骨細胞分化 / ケミカルバイオロジー / RANKL / 骨疾患 / 低分子化合物 / 骨粗鬆症 / 骨転移 / 構造活性相関
Outline of Final Research Achievements	The number of bone-related disease patients is increasing in Japan. At present, bisphosphonates are widely used for these diseases, but their severe s ...

Research Products of this project	Journal Article (16 results, of which Peer Reviewed: 16 results, Acknowledgement Compliant: 6 results, Open Access: 2 results) Presentation (38 results, of which Invited: 3 results) Remarks (3 results)

5. Development of a new strategy for pancreatic islet transplantation by molecular targeting agents

Research Project

Research Category	Grant-in-Aid for Scientific Research (B)
Research Field	General surgery
Research Institution	Hokkaido University
Principal Investigator	YAMASHITA Kenichiro 北海道大学, 医学(系)研究科(研究院), 特任教授
Project Period (FY)	2011-04-01 – 2014-03-31Completed
Keywords	膵ラ氏島移植 / 分子標的治療 / NF-κB / CD40
Research Abstract	Pancreatic islet transplantation (PIT) is an ideal cell-based therapy for type I diabetes. However, transplanted islets are injured immediately after ...

Research Products of this project	Journal Article (10 results, of which Peer Reviewed: 10 results) Presentation (6 results)

6. Bio-imaging of peritoneal metastasis and molecular design of inhibitors

Research Project

Research Category	Grant-in-Aid for Scientific Research (B)
Research Field	Chemical biology
Research Institution	Aichi Medical University (2012-2013) Keio University (2011)
Principal Investigator	UMEZAWA Kazuo 愛知医科大学, 医学部, 教授
Project Period (FY)	2011-04-01 – 2014-03-31Completed
Keywords	分子デザイン / バイオイメージング / 腹腔内転移 / 浸潤 / 遊走 / NF-kappa B / DHMEQ / DTCM-glutarimide / migracin / Exo-ene EQ / pyrapaxilline / 卵巣がん / 転移 / アノイキス / メラノーマ / 卵巣癌 / NF-κB / 探索プローブ / 標的タンパク質 / 光プローブ
Research Abstract	Purpose of this project is to discover new metastasis inhibitors of low molecular weight from nature and by molecular design. Especially, peritoneal m ...

Research Products of this project	Journal Article (64 results, of which Peer Reviewed: 57 results) Presentation (28 results, of which Invited: 5 results) Remarks (5 results)

7. Molecular design and synthesis of soluble NF-κB inhibitor and suppression of ovarian carcinoma

Research Project

Research Category	Grant-in-Aid for Scientific Research (C)
Research Field	Chemical biology
Research Institution	Keio University
Principal Investigator	UMEZAWA Kazuo Keio University
Project Period (FY)	2008 – 2010Completed
Keywords	DHMEQ / NF-κB / 卵巣癌 / 分子デザイン / 腹腔内播種 / 浸潤 / 転移 / 抗癌剤
Research Abstract	Our newly found NF-κB inhibitor DHMEQ is very specific and ameliorates many disease models in animal experiments. However, it is hardly soluble to mos ...

Research Products of this project	Journal Article (53 results, of which Peer Reviewed: 51 results) Presentation (70 results) Book (9 results) Remarks (4 results) Patent(Industrial Property Rights) (3 results)

8. Studies on thrombophilic diathesis and development of a novel molecular-targeting therapy in antiphospholipid syndrome

Research Project

Research Category	Grant-in-Aid for Scientific Research (C)
Research Field	膠原病・アレルギー・感染症内科学
Research Institution	Tokyo Medical and Dental University
Principal Investigator	KUBOTA Tetsuo Tokyo Medical and Dental University
Project Period (FY)	2008 – 2010Completed
Keywords	抗リン脂質抗体症候群 / 抗β2-グリコプロテインI抗体 / 動物モデル / NF-kappaB / 抗β2グリコプロテインI抗体 / シグナル伝達阻害薬 / 血小板機能 / ケモカイン
Research Abstract	IgG fraction of patients with systemic lupus erythematosus (SLE) who had anti-β2-glycoprotein I (β2-GPI) antibodies induced expression of inflammatory ...

Research Products of this project	Journal Article (8 results, of which Peer Reviewed: 2 results) Presentation (7 results) Remarks (2 results)

9. Development of safe liver transplantation by modulation of transcription factor, nuclear factor kappa B (NF-kB)

Research Project

Research Category	Grant-in-Aid for Scientific Research (A)
Research Field	General surgery
Research Institution	Hokkaido University
Principal Investigator	藤堂省 Hokkaido University
Project Period (FY)	2006 – 2008Completed
Keywords	NF-kB / 免疫抑制 / 臓器保存 / 虚血再灌流障害 / 臓器移植 / 肝移植 / 拒絶反応 / NF kappa B / 虚血再灌流 / NF-KB / DHMEQ / 虚血・再かん流障害
Research Abstract	移植後の拒絶反応と炎症を軽減するために、新規NF-kB阻害剤Qの効果、投与法、剤型を検討した。拒絶、炎症に関わる免疫担当細胞の抑制や、小動物の肝、小腸、心、膵島細胞移植および虚血再灌流で有効性が確認された。また、新規臓器保存液を試作し、肝および多くの細胞や心移植における冷保存障害の軽減に成功した。臨 ...

Research Products of this project	Journal Article (20 results, of which Peer Reviewed: 16 results) Presentation (50 results)

10. 力学的刺激による毛細血管3次元ネットワーク形成の促進と再生医療への応用

Research Project

Research Category	Grant-in-Aid for Exploratory Research
Research Field	Biomedical engineering/Biological material science
Research Institution	Keio University
Principal Investigator	谷下一夫慶應義塾大学, 理工学部, 教授
Project Period (FY)	2005 – 2006Completed
Keywords	内皮細胞 / 毛細血管 / 再生医療 / 血管新生 / 内皮前駆細胞 / 低酸素 / コラーゲンゲル / バイオメカニクス / 基質 / コラーゲン / 足場構造
Research Abstract	再生臓器の実現のためには、細胞集合体への酸素供給のための血管ネットワークが必要となり、特に3次元細胞組織中に深く侵入するような3次元のネットワーク形成が必要である。本研究では、3次元的に血管ネットワークが深く侵入する力学的刺激の最適条件、さらに内皮前駆細胞を用いた場合や、増殖因子(bFGF,VEGF ...

Research Products of this project	Journal Article (9 results) Book (1 results)

11. Pathophysiological role of NF k B and the efficacy of a novel NF K B inhibitor in urological cancers

Research Project

Research Category	Grant-in-Aid for Scientific Research (B)
Research Field	Urology
Research Institution	Keio University
Principal Investigator	MURAI Masaru Keio University, School of Medicine, Professor
Project Period (FY)	2004 – 2006Completed
Keywords	NF-κB / urological malignancy / apoptosis / metastasis / cytokine
Research Abstract	NF-κB is a transcription factor consisting mainly of p65 and p50 proteins and induces inflammatory cytokines and anti-apoptotic proteins. Activation o ...

Research Products of this project	Journal Article (19 results)

12. 天然由来シグナル伝達阻害物質の探索と医薬への応用

Research Project

Research Category	Grant-in-Aid for Scientific Research on Priority Areas
Review Section	Science and Engineering
Research Institution	Keio University
Principal Investigator	梅澤一夫 (梅沢一夫) Keio University
Project Period (FY)	2004 – 2007Completed
Keywords	癌 / 生理活性物質 / シグナル伝達 / 微生物 / 有機化学 / 生理活性 / NF-κB / エポキシキノマイシン / DHMEQ / コノフィリン / インスリン / ヘプタデプシン / リポ多糖
Research Abstract	今年度はNF-κB阻害物質(-)-DHMEQの標的分子を解明することができた。1)(-)-DHMEQの標的分子の解明。私達が発見した(-)-DHMEQは様々な病態動物モデルで強い治療効果を示した。しかし、その標的分子は未解明であった。今回、(-)-DHMEQはp65に直接結合して、DNA結合能を失わ ...

Research Products of this project	Journal Article (59 results, of which Peer Reviewed: 11 results) Presentation (1 results) Book (1 results) Remarks (1 results) Patent(Industrial Property Rights) (2 results)

13. Screening for selective acidic sphyngomyelinase inhibitor using microbial product

Research Project

Research Category	Grant-in-Aid for Scientific Research (C)
Research Field	Living organism molecular science
Research Institution	Microbial Chemistry Research Foundation
Principal Investigator	IKEDA Yoko Microbial Chemistry Research Foundation, Microbial Chemistry Research Center, Bioactive Molecules Research Group, a research chemist
Project Period (FY)	2003 – 2005Completed
Keywords	microbial product / acidic sphyngomyelinase / inhibitor
Research Abstract	In the course of our screening for acidic sphingomyelinase inhibitors we isolated three xanthone compounds, α-mangostin, cowanine and cowanol from the ...

Research Products of this project	Journal Article (8 results)

14. 癌細胞のアポトーシス耐性および分化誘導耐性克服物質の探索

Research Project

Research Category	Grant-in-Aid for Scientific Research on Priority Areas
Review Section	Science and Engineering
Research Institution	Keio University
Principal Investigator	梅澤一夫 (梅沢一夫) 慶應義塾大学, 理工学部, 教授
Project Period (FY)	2001 – 2002Completed
Keywords	応用微生物 / 癌 / 細胞・組織 / 糖尿病 / 有機化学
Research Abstract	1)NF-κB阻害剤DHMEQの抗癌活性と接着因子発現阻害

Research Products of this project	Publications (12 results)

15. 微生物、植物由来アポトーシス耐性克服物質の探索

Research Project

Research Category	Grant-in-Aid for Scientific Research on Priority Areas (A)
Review Section	Science and Engineering
Research Institution	Keio University
Principal Investigator	梅沢一夫慶應義塾大学, 理工学部, 教授
Project Period (FY)	2000Completed
Keywords	アポトーシス / 抗癌剤 / 放線菌 / 植物 / スクリーニング / 生合成 / 膵腺癌細胞
Research Abstract	ヒト固形癌細胞のアポトーシス耐性に注目し、耐性細胞に直接アポトーシスを誘導する物質、およびアポトーシス耐性を誘導するシグナル伝達の阻害物質を微生物、植物の二次代謝産物および誘導体から探索した。

Research Products of this project	Publications (6 results)

16. 画像化能を有する生体機能探査分子の設計原理の開発

Research Project

Research Category	Grant-in-Aid for Scientific Research (C)
Research Field	医薬分子機能学
Research Institution	The University of Tokyo
Principal Investigator	樋口恒彦東京大学, 大学院・薬学系研究科, 助教授
Project Period (FY)	1999Completed
Keywords	生体機能 / 機能性分子 / 螢光 / シグナル伝達 / 画像 / 合成化学
Research Abstract	本企画調査は生体機能を画像化する能力を有する低分子化合物を開発し、生体の動的機能解明へ応用を行う研究分野に関し、今後の特定領域研究への立ち上げの準備段階として行った。

Research Products of this project	Publications (6 results)

17. Molecular Design of Ras Farnesyltransferase Inhibitors

Research Project

Research Category	Grant-in-Aid for Scientific Research (B)
Research Field	医薬分子機能学
Research Institution	Kumamoto University
Principal Investigator	OTSUKA Masami Kumamoto University, Graduate School of Pharmaceutical Sciences, Professor
Project Period (FY)	1999 – 2001Completed
Keywords	man-made chelator / farnesyltransferase / oncogene / Ras protein
Research Abstract	Oncogene ras is found in many mammalian cancer cells and the encoded protein Ras is an important target for anticancer agents. The farnesylation of th ...

Research Products of this project	Publications (13 results)

18. がん細胞分化機構の分子生物学的解明と分化誘導療法の臨床応用に関する基礎的研究

Research Project

Research Category	Grant-in-Aid for Scientific Research on Priority Areas
Research Institution	Hamamatsu University School of Medicine
Principal Investigator	大野竜三浜松医科大学, 医学部, 教授
Project Period (FY)	1996Completed
Keywords	レチノイン酸 / 分化誘導療法 / 急性前骨髄球性白血病 / Am-80 / 細胞内レチノイン酸結合蛋白 / PML / RARA / 亜砒酸 / レチノイドアンタゴニスト
Research Abstract	全トランス型レチノイン酸(ATRA)による分化誘導療法は急性前骨髄球性白血病(APL)に90%以上の有効性を示すがATRA治療後の再発例には20%以下の再寛解率しか示さない。班員が創製した新レチノイドAm-80はATRA耐性細胞において増加している細胞内レチノイン酸結合蛋白とは親和性を示さないため、 ...

Research Products of this project	Publications (6 results)

19. 糖鎖生合成修飾による転移の抑制

Research Project

Research Category	Grant-in-Aid for Scientific Research on Priority Areas
Research Institution	Keio University
Principal Investigator	梅沢一夫慶応義塾大学, 理工学部, 教授
Project Period (FY)	1995Completed
Keywords	がん遺伝子 / コノフィリン / レクチン / 浸潤 / 子宮体がん / H抗原 / メラノーマ
Research Abstract	本研究ではRas活性阻害剤による糖鎖構造の修飾とがん細胞浸潤の抑制を調べた。

Research Products of this project	Publications (8 results)

20. 糖鎖生合成修飾による転移の抑制

Research Project

Research Category	Grant-in-Aid for Scientific Research on Priority Areas
Research Institution	Keio University
Principal Investigator	梅沢一夫慶應義塾大学, 理工学部, 教授
Project Period (FY)	1994Completed
Keywords	エピサイクロフェリトール / α-グルコシダーゼ / マウスメラノーマ / ルイス肺がん / Con A結合蛋白 / 浸潤 / 転移
Research Abstract	糖鎖プロセッシングに関与する種々のグリコシダーゼ阻害物質およびがん遺伝子作用阻害物質を微生物、植物から探索し、転移抑制剤を開発することおよび阻害剤による細胞表面糖鎖の変化を解析することが目的である。

Research Products of this project	Publications (8 results)

Project Period (Start Year [FY])

1. Elucidation of the mechanism of hepatitis B virus entry and control of infection by entry inhibitors Research Project

伊藤 清顕 愛知医科大学, 医学部, 教授

2. Screening of cancer cell 3D invasion inhibitors from microbial metabolites Research Project

Umezawa Kazuo 愛知医科大学, 医学部, 教授

3. Screening of NF-kappa B inhibitors having new core structure and application to aggressive cancer treatment Research Project

Umezawa Kazuo 愛知医科大学, 医学部, 教授

4. Development of novel drug for bone-related diseases using Pirin inhibitors Research Project

SIMIZU Siro 慶應義塾大学, 理工学部, 准教授

5. Development of a new strategy for pancreatic islet transplantation by molecular targeting agents Research Project

YAMASHITA Kenichiro 北海道大学, 医学(系)研究科(研究院), 特任教授

6. Bio-imaging of peritoneal metastasis and molecular design of inhibitors Research Project

UMEZAWA Kazuo 愛知医科大学, 医学部, 教授

7. Molecular design and synthesis of soluble NF-κB inhibitor and suppression of ovarian carcinoma Research Project

UMEZAWA Kazuo Keio University

8. Studies on thrombophilic diathesis and development of a novel molecular-targeting therapy in antiphospholipid syndrome Research Project

KUBOTA Tetsuo Tokyo Medical and Dental University

9. Development of safe liver transplantation by modulation of transcription factor, nuclear factor kappa B (NF-kB) Research Project

藤堂 省 Hokkaido University

10. 力学的刺激による毛細血管3次元ネットワーク形成の促進と再生医療への応用 Research Project

谷下 一夫 慶應義塾大学, 理工学部, 教授

11. Pathophysiological role of NF k B and the efficacy of a novel NF K B inhibitor in urological cancers Research Project

MURAI Masaru Keio University, School of Medicine, Professor

12. 天然由来シグナル伝達阻害物質の探索と医薬への応用 Research Project

梅澤 一夫 (梅沢 一夫) Keio University

13. Screening for selective acidic sphyngomyelinase inhibitor using microbial product Research Project

IKEDA Yoko Microbial Chemistry Research Foundation, Microbial Chemistry Research Center, Bioactive Molecules Research Group, a research chemist

14. 癌細胞のアポトーシス耐性および分化誘導耐性克服物質の探索 Research Project

梅澤 一夫 (梅沢 一夫) 慶應義塾大学, 理工学部, 教授

15. 微生物、植物由来アポトーシス耐性克服物質の探索 Research Project

梅沢 一夫 慶應義塾大学, 理工学部, 教授

16. 画像化能を有する生体機能探査分子の設計原理の開発 Research Project

樋口 恒彦 東京大学, 大学院・薬学系研究科, 助教授

17. Molecular Design of Ras Farnesyltransferase Inhibitors Research Project

OTSUKA Masami Kumamoto University, Graduate School of Pharmaceutical Sciences, Professor

18. がん細胞分化機構の分子生物学的解明と分化誘導療法の臨床応用に関する基礎的研究 Research Project

大野 竜三 浜松医科大学, 医学部, 教授

19. 糖鎖生合成修飾による転移の抑制 Research Project

梅沢 一夫 慶応義塾大学, 理工学部, 教授

20. 糖鎖生合成修飾による転移の抑制 Research Project

梅沢 一夫 慶應義塾大学, 理工学部, 教授

1. Elucidation of the mechanism of hepatitis B virus entry and control of infection by entry inhibitors

Research Project

伊藤清顕愛知医科大学, 医学部, 教授

2. Screening of cancer cell 3D invasion inhibitors from microbial metabolites

Research Project

3. Screening of NF-kappa B inhibitors having new core structure and application to aggressive cancer treatment

Research Project

4. Development of novel drug for bone-related diseases using Pirin inhibitors

Research Project

5. Development of a new strategy for pancreatic islet transplantation by molecular targeting agents

Research Project

6. Bio-imaging of peritoneal metastasis and molecular design of inhibitors

Research Project

7. Molecular design and synthesis of soluble NF-κB inhibitor and suppression of ovarian carcinoma

Research Project

8. Studies on thrombophilic diathesis and development of a novel molecular-targeting therapy in antiphospholipid syndrome

Research Project

9. Development of safe liver transplantation by modulation of transcription factor, nuclear factor kappa B (NF-kB)

Research Project

藤堂省 Hokkaido University

10. 力学的刺激による毛細血管3次元ネットワーク形成の促進と再生医療への応用

Research Project

谷下一夫慶應義塾大学, 理工学部, 教授

11. Pathophysiological role of NF k B and the efficacy of a novel NF K B inhibitor in urological cancers

Research Project

12. 天然由来シグナル伝達阻害物質の探索と医薬への応用

Research Project

梅澤一夫 (梅沢一夫) Keio University

13. Screening for selective acidic sphyngomyelinase inhibitor using microbial product

Research Project

14. 癌細胞のアポトーシス耐性および分化誘導耐性克服物質の探索

Research Project

梅澤一夫 (梅沢一夫) 慶應義塾大学, 理工学部, 教授

15. 微生物、植物由来アポトーシス耐性克服物質の探索

Research Project

梅沢一夫慶應義塾大学, 理工学部, 教授

16. 画像化能を有する生体機能探査分子の設計原理の開発

Research Project

樋口恒彦東京大学, 大学院・薬学系研究科, 助教授

17. Molecular Design of Ras Farnesyltransferase Inhibitors

Research Project

18. がん細胞分化機構の分子生物学的解明と分化誘導療法の臨床応用に関する基礎的研究

Research Project

大野竜三浜松医科大学, 医学部, 教授

19. 糖鎖生合成修飾による転移の抑制

Research Project

梅沢一夫慶応義塾大学, 理工学部, 教授

20. 糖鎖生合成修飾による転移の抑制

Research Project

梅沢一夫慶應義塾大学, 理工学部, 教授