Development of HIF inhibitor as anti-angiogenic agents

• Project/Area Number: 22790113
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Drug development chemistry
• Research Institution: Gakushuin University
• Principal Investigator: BAN Hyunseung 学習院大学, 理学部, 助教 (60433710)
• Co-Investigator(Renkei-kenkyūsha): NAKAMURA Hiroyuki 学習院大学, 理学部, 教授 (30274434)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 血管新生 / 低酸素 / 低酸素誘導因子

Research Abstract

In this research, we developed HIF inhibitors as anti-angiogenic agents and clarified the mechanism of action. We found that compound GN26361 suppressed HIF-1αprotein level via inhibition of HSP60 under hypoxic conditions.

Research Products

• [Journal Article] Identification of heat shock protein 60 as the regulator of the hypoxia-inducible factor subunit HIF-1a (2012)
  • Author(s): Hyun Seung Ban, et. al
  • Journal Title: Pure and Applied Chemistry Volume: (In print)
  • Peer Reviewed
• [Journal Article] Design and synthesis of fluorescence-labeled close-dodecaborate lipid: its liposome formation and in vivo imaging targeting of tumors for boron neutron capture therapy (2012)
  • Author(s): Nakamura H, Ueda N, Bam HS, Ueno M, Tachikawa S
  • Journal Title: Org. Biomol. Chem. Volume: 10 Issue: 7 Pages: 1374-80
  • DOI: 10.1039/c1ob06500a
  • Peer Reviewed
• [Journal Article] Hypoxia-inducible factor inhibitors : A survey of recent patented compounds(2004-2010) (2011)
  • Author(s): Hyun Seung Ban, Yoshikazu Uto, Hiroyuki Nakamura
  • Journal Title: Expert Opinion on Therapeutic Patents Volume: 21(2) Issue: 2 Pages: 131-146
  • DOI: 10.1517/13543776.2011.547477
  • Peer Reviewed
• [Journal Article] Hypoxia-inducible factor inhibitors : A survey of recent patented compounds (2004-2010) (2011)
  • Author(s): Hyun Seung S.Ban, Yoshikazu Uto, Hiroyuki Nakamura
  • Journal Title: Expert Opinion on Therapeutic Patents Volume: 21(2) Pages: 131-146
  • Peer Reviewed
• [Journal Article] Identification of HSP60 as a primary target of o-carboranylphenoxyacet anilide, an HIF-1α inhibitor (2010)
  • Author(s): Hyun Seung Ban, Kazuki Shimizu, Hidemitsu Minegishi, Hiroyuki Nakamura
  • Journal Title: Journal of American Chemistry Society Volume: 132(34) Issue: 34 Pages: 11870-11871
  • DOI: 10.1021/ja104739t
  • Peer Reviewed
• [Journal Article] Suppression of hypoxiainduced HIF-1αaccumulation by VEGFR inhibitors : Different profiles of AAL993 versus SU5416 and KRN633 (2010)
  • Author(s): Hyun Seung Ban, Masaharu Uno, Hiroyuki Nakamura
  • Journal Title: Cancer Letters Volume: 296(1) Pages: 17-26
  • URL: http://dx.doi.org/10.1016/j.canlet.2010.03.010
  • Peer Reviewed
• [Journal Article] Boroncontaining phenoxyacetanilide deri vatives as hypoxia-inducible Factor(HIF)-1α inhibitors (2010)
  • Author(s): Kazuki Shimizu, Minako Maruyama, Yuka Yasui, Hidemitsu Minegishi, Hyun Seung Ban, Hiroyuki Nakamura
  • Journal Title: Bioorganic and Medicinal Chemistry Letters Volume: 20(4) Pages: 1453-1456
  • URL: http://dx.doi.org/10.1016/j.bmcl.2009.12.037
  • Peer Reviewed
• [Journal Article] Identification of HSP60 as a primary target of o-carboranylphenoxyacetanilide, an HIF-1α inhibitor (2010)
  • Author(s): Hyun Seung Ban, Kazuki Shimizu, Hidemitsu Minegishi, Hiroyuki Nakamura
  • Journal Title: Journal of American Chemistry Society Volume: 132(34) Pages: 11870-11871
  • Peer Reviewed
• [Journal Article] Suppression of hypoxia-induced HIF-1α accumulation by VEGFR inhibitors : Different profiles of AAL993 versus SU5416 and KRN633 (2010)
  • Author(s): Hyun Seung Ban, Masaharu Uno, Hiroyuki Nakamura
  • Journal Title: Cancer Letters Volume: 296(1) Pages: 17-26
  • Peer Reviewed
• [Presentation] HIF阻害剤GN26361の作用機序の解明 (2011)
  • Author(s): 潘鉉承、清水一希、峯岸秀充、中村浩之
  • Organizer: 第8回がんとハイポキシア研究会
  • Place of Presentation: 札幌
• [Presentation] HIF阻害剤GN26361の作用機序:HSP60阻害によるHIF-1αの安定化抑 (2011)
  • Author(s): 潘鉉承, 外3名
  • Organizer: 日本ケミカルバイオロジー学会第6回年会
  • Place of Presentation: 東京
• [Presentation] HIF阻害剤GN26361の作用機序 (2011)
  • Author(s): 潘鉉承、清水一希、峯岸秀充、中村浩之
  • Organizer: 第131年回日本薬学会
  • Place of Presentation: 静岡
• [Presentation] Action mechanism of HIF-1α inhibitor GN26361 : Identification of target protein with multifunctional molecular probe (2010)
  • Author(s): H. Ban、K. Shimizu、H. Minegishi、H. Nakamura
  • Organizer: 2010環太平洋国際化学会議
  • Place of Presentation: Honolulu(ハワイ)
• [Presentation] 低酸素誘導因子(HIF)阻害剤GN26361の作用機序の解明 (2010)
  • Author(s): 潘鉉承、清水一希、峯岸秀充、中村浩之
  • Organizer: 第14回日本がん分子標的治療学会学術集会
  • Place of Presentation: 東京
• [Presentation] カルボラン含有小分子化合物GN26361による低酸素誘導因子(HIF)阻害と作用機序 (2010)
  • Author(s): 潘鉉承、清水一希、峯岸秀充、中村浩之
  • Organizer: 第7回日本中性子捕捉療法学会学術集会
  • Place of Presentation: 東京
• [Presentation] HIF阻害剤GN26361の標的分子HSP60の同定 (2010)
  • Author(s): 潘鉉承、清水一希、峯岸秀充、中村浩之
  • Organizer: 第29回メディシナルケミストリーシンポジウム
  • Place of Presentation: 京都
• [Presentation] Action mechanism of HIF-1α inhibitor GN26361 : identification of target protein with multifunctional molecular probe (2010)
  • Author(s): Hyun Seung Ban, Kazuki Shimizu, Hidemitsu Minegishi, Hiroyuki Nakamura
  • Organizer: 2010環太平洋国際化学会議
  • Place of Presentation: ホノルル
• [Presentation] カルボラン含有小分子化合物GN26361による低酸素誘導因子(HIF)阻害と作用機序 (2010)
  • Author(s): 潘鉉承、清水一希、峯岸秀充、中村浩之
  • Organizer: 第7回日本中性子捕捉療法学会学術大会
  • Place of Presentation: 東京