Discovery and Investigation of Novel Angiogenesis Inhibitors Among Existing Drugs

现有药物中新型血管生成抑制剂的发现和研究

基本信息

  • 批准号:
    7537218
  • 负责人:
  • 金额:
    $ 34.03万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2008
  • 资助国家:
    美国
  • 起止时间:
    2008-01-01 至 2012-12-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Angiogenesis, the formation of new blood vessels, plays an essential role in the pathogenesis of several important human diseases including cancer. Inhibition of angiogenesis is a promising strategy to control tumor growth and metastasis. The main objective of this application is to discover and develop new angiogenesis inhibitors from existing clinical drugs and to elucidate the molecular mechanisms of angiogenesis inhibition by two angiogenesis inhibitors previously discovered to facilitate the development of the next generation of angiogenesis inhibitors for the treatment of cancer. In preliminary studies, we have assembled a library of mostly FDA-approved clinical drugs and screened it in an endothelial cell proliferation assay. We have identified several potent hits including an immunosuppressant drug and an antifungal drug. We have further demonstrated the efficacy of both drugs in blocking VEGF- and bFGF- mediated angiogenesis in vivo. In this study, we propose to further expand the clinical drug library to include more FDA-approved drugs as well as those that have reached phase II clinical trials to identify additional inhibitors of angiogenesis and make the library available to the wider scientific community to screen in other cellular models. We will further characterize the function of the immunosuppressant target in both T cell activation and angiogenesis in mice and humans. We will attempt to identify new inhibitors for the immunosuppressant target to reduce the toxicity of the existing drug by a combination of combinatorial click chemistry and high-throughput screening. We will perform experiments to verify a potential target for the antifungal drug in endothelial cells and perform SAR studies on the antifungal drug in attempts to prepare affinity reagents to identify and validate its target in endothelial cells and to improve the efficacy of the drug for inhibition of angiogenesis and tumor growth. Angiogenesis, the formation of new blood vessels, plays an essential role in several important human diseases including cancer. The main objective of this application is to discover and develop new angiogenesis inhibitors from existing drugs to accelerate the translation of basic research findings into new cancer treatments and to facilitate the development of future generations of anti-angiogenic drugs with improved specificity and lower toxicity.
描述(由申请人提供):血管生成,即新血管的形成,在包括癌症在内的几种重要人类疾病的发病机制中起重要作用。抑制血管生成是控制肿瘤生长和转移的一个有前途的策略。本申请的主要目的是从现有临床药物中发现和开发新的血管生成抑制剂,并阐明先前发现的两种血管生成抑制剂抑制血管生成的分子机制,以促进下一代血管生成抑制剂的开发,用于治疗癌症。在初步研究中,我们已经组装了一个大多数FDA批准的临床药物库,并在内皮细胞增殖试验中对其进行筛选。我们已经确定了几种有效的药物,包括免疫抑制剂和抗真菌药物。我们已经进一步证明了这两种药物在体内阻断VEGF和bFGF介导的血管生成的功效。在这项研究中,我们建议进一步扩大临床药物库,以包括更多FDA批准的药物以及已达到II期临床试验的药物,以确定其他血管生成抑制剂,并使该库可供更广泛的科学界在其他细胞模型中筛选。我们将进一步表征免疫抑制剂靶标在小鼠和人类中T细胞活化和血管生成中的功能。我们将尝试通过组合点击化学和高通量筛选的组合来确定免疫抑制剂靶点的新抑制剂以降低现有药物的毒性。我们将进行实验以验证抗真菌药物在内皮细胞中的潜在靶点,并对抗真菌药物进行SAR研究,试图制备亲和试剂以识别和验证其在内皮细胞中的靶点,并提高药物抑制血管生成和肿瘤生长的功效。血管生成,即新血管的形成,在包括癌症在内的几种重要的人类疾病中起着至关重要的作用。该申请的主要目的是从现有药物中发现和开发新的血管生成抑制剂,以加速将基础研究成果转化为新的癌症治疗方法,并促进未来几代具有更高特异性和更低毒性的抗血管生成药物的开发。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Jun O. Liu其他文献

Binding of thalidomide to alpha1-acid glycoprotein may be involved in its inhibition of tumor necrosis factor alpha production.
沙利度胺与 α1-酸性糖蛋白的结合可能参与其抑制肿瘤坏死因子 α 的产生。
suppresses the oncogenic activity of YAP YAP complex - Genetic and pharmacological disruption of the TEAD
抑制 YAP YAP 复合物的致癌活性 - TEAD 的遗传和药理学破坏
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Y. Liu;Bo Huang;J. Shim;Qian Chen;Se;Robert A. Anders;Jun O. Liu;Duojia Pan
  • 通讯作者:
    Duojia Pan
Phase of the Cell Cycle 1 IL-2-Dependent T Cell Proliferation at the G Immunosuppressant, Inhibits Sanglifehrin A, a Novel Cyclophilin-Binding
细胞周期 1 阶段 IL-2 依赖性 T 细胞在 G 处增殖 免疫抑制剂抑制 Sanglifehrin A(一种新型亲环蛋白结合)
  • DOI:
  • 发表时间:
    2001
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Ling;Jun O. Liu
  • 通讯作者:
    Jun O. Liu
Selective inhibition of amino-terminal methionine processing by TNP-470 and ovalicin in endothelial cells.
TNP-470 和卵黄素在内皮细胞中选择性抑制氨基末端甲硫氨酸加工。
  • DOI:
  • 发表时间:
    1999
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Benjamin E. Turk;Eric C. Griffith;Susan M. Wolf;Klaus Biemann;Yie;Jun O. Liu
  • 通讯作者:
    Jun O. Liu
Girolline is a sequence context-selective modulator of eIF5A activity
吉罗啉是一种 eIF5A 活性的序列上下文选择性调节剂
  • DOI:
    10.1038/s41467-024-54838-2
  • 发表时间:
    2025-01-10
  • 期刊:
  • 影响因子:
    15.700
  • 作者:
    Tilman Schneider-Poetsch;Yongjun Dang;Wakana Iwasaki;Mayumi Arata;Yuichi Shichino;Ali Al Mourabit;Celine Moriou;Daniel Romo;Jun O. Liu;Takuhiro Ito;Shintaro Iwasaki;Minoru Yoshida
  • 通讯作者:
    Minoru Yoshida

Jun O. Liu的其他文献

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{{ truncateString('Jun O. Liu', 18)}}的其他基金

Characterization of A Novel Proteasome Inhibitor
新型蛋白酶体抑制剂的表征
  • 批准号:
    10597711
  • 财政年份:
    2022
  • 资助金额:
    $ 34.03万
  • 项目类别:
Targeting Glucose Transporters Using Rapafucins
使用雷帕夫星靶向葡萄糖转运蛋白
  • 批准号:
    10335197
  • 财政年份:
    2020
  • 资助金额:
    $ 34.03万
  • 项目类别:
Targeting Glucose Transporters Using Rapafucins
使用雷帕夫星靶向葡萄糖转运蛋白
  • 批准号:
    10557907
  • 财政年份:
    2020
  • 资助金额:
    $ 34.03万
  • 项目类别:
Studies of the Antifungal Drug Itraconazole As A Novel Inhibitor of Angiogenesis
抗真菌药物伊曲康唑作为新型血管生成抑制剂的研究
  • 批准号:
    8817767
  • 财政年份:
    2015
  • 资助金额:
    $ 34.03万
  • 项目类别:
Generation and Proteome-Wide Screening of Hybrid Combinatorial Libraries
混合组合文库的生成和全蛋白质组筛选
  • 批准号:
    8520275
  • 财政年份:
    2010
  • 资助金额:
    $ 34.03万
  • 项目类别:
Generation and Proteome-Wide Screening of Hybrid Combinatorial Libraries
混合组合文库的生成和全蛋白质组筛选
  • 批准号:
    8323364
  • 财政年份:
    2010
  • 资助金额:
    $ 34.03万
  • 项目类别:
Generation and Proteome-Wide Screening of Hybrid Combinatorial Libraries
混合组合文库的生成和全蛋白质组筛选
  • 批准号:
    8151102
  • 财政年份:
    2010
  • 资助金额:
    $ 34.03万
  • 项目类别:
Generation and Proteome-Wide Screening of Hybrid Combinatorial Libraries
混合组合文库的生成和全蛋白质组筛选
  • 批准号:
    7979320
  • 财政年份:
    2010
  • 资助金额:
    $ 34.03万
  • 项目类别:
Generation and Proteome-Wide Screening of Hybrid Combinatorial Libraries
混合组合文库的生成和全蛋白质组筛选
  • 批准号:
    8705479
  • 财政年份:
    2010
  • 资助金额:
    $ 34.03万
  • 项目类别:
Discovery and Investigation of Novel Angiogenesis Inhibitors Among Existing Drugs
现有药物中新型血管生成抑制剂的发现和研究
  • 批准号:
    7351352
  • 财政年份:
    2008
  • 资助金额:
    $ 34.03万
  • 项目类别:

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Sexual dimorphism in antigen-independent angiogenesis inhibition of IgG1 antibodies
IgG1 抗体的抗原非依赖性血管生成抑制中的性别二态性
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鉴定 p53 抑制血管生成的新机制
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