高级检索

靶向HIF-1α/p300蛋白-蛋白相互作用抑制剂的研究进展

莫小飞, 徐晓莉, 王亚楼, 尤启冬

莫小飞, 徐晓莉, 王亚楼, 尤启冬. 靶向HIF-1α/p300蛋白-蛋白相互作用抑制剂的研究进展[J]. 中国药科大学学报, 2017, 48(5): 515-522. DOI: 10.11665/j.issn.1000-5048.20170502
引用本文: 莫小飞, 徐晓莉, 王亚楼, 尤启冬. 靶向HIF-1α/p300蛋白-蛋白相互作用抑制剂的研究进展[J]. 中国药科大学学报, 2017, 48(5): 515-522. DOI: 10.11665/j.issn.1000-5048.20170502
shu
MO Xiaofei, XU Xiaoli, WANG Yalou, YOU Qidong. Advances in the HIF-1α/p300 protein-protein interaction inhibitors[J]. Journal of China Pharmaceutical University, 2017, 48(5): 515-522. DOI: 10.11665/j.issn.1000-5048.20170502
Citation: MO Xiaofei, XU Xiaoli, WANG Yalou, YOU Qidong. Advances in the HIF-1α/p300 protein-protein interaction inhibitors[J]. Journal of China Pharmaceutical University, 2017, 48(5): 515-522. DOI: 10.11665/j.issn.1000-5048.20170502
shu

靶向HIF-1α/p300蛋白-蛋白相互作用抑制剂的研究进展

  • 1.

    中国药科大学江苏省药物分子设计与成药性优化重点实验室

  • 2.

    中国药科大学药物化学系

基金项目: 国家自然科学基金资助项目(NO.81502990,No.81573346)；江苏省自然科学基金资助项目(No.BK20150691)

Advances in the HIF-1α/p300 protein-protein interaction inhibitors

摘要

    摘要
  • 摘要: 缺氧诱导因子-1α(hypoxia induced factor-1α，HIF-1α)是肿瘤适应缺氧微环境的重要调节因子。它调控细胞增殖与存活、新陈代谢、血管生成、入侵与转移等相关行为的100多个靶基因，而HIF-1α/p300是调控这些下游基因表达的重要复合物，靶向HIF-1α/p300蛋白-蛋白相互作用展开抑制剂的开发成为抗肿瘤药物研究的又一热点。本文对HIF-1α信号通路、HIF-1α/p300蛋白-蛋白相互作用的结合模式以及近年HIF-1α/p300蛋白-蛋白相互作用抑制剂的研究进展进行了综述，为该类抑制剂的设计提供参考。
    Abstract: Hypoxia induced factor-1α(HIF-1α)is a key regulation factor that helps tumor adapt itself to the hypoxia microenvironment. It regulates the expression of more than 100 target genes that control cell proliferation and survival, metabolism, angiogenesis, invasion and metastasis. HIF-1α/p300, a core complex that regulates downstream genes expression, is considered as a potential antitumor target. This review summarizes HIF-1α signal pathway, the binding mode of HIF-1α/p300 protein-protein interaction and recent development on the HIF-1α/p300 protein-protein interaction inhibitors, which provides reference to the design of this kind of inhibitors.
    • HTML全文
    • 参考文献(30)
  • [1] Harris AL.Hypoxia—a key regulatory factor in tumor growth[J]. Nat Rev Cancer,2002,2(1):38-47.
    [2] Semenza GL.HIF-1:upstream and downstream of cancer metabolism[J]. Curr Opin Genet Dev,2010,20(1):51-56.
    [3] Arany Z,Huang LE,Eckner R,et al.An essential role for p300/CBP in the cellular response to hypoxia[J]. Proc Natl Acad Sci U S A,1996,93(23):12969-12973.
    [4] Kamei Y,Xu L,Heinzel T,et al.A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors[J]. Cell,1996, 85(3):403-414.
    [5] Vo N,Goodman RH.CREB-binding protein and p300 in transcriptional regulation[J]. J Biol Chem,2001,276(17):13505-13508.
    [6] Majmundar AJ,Wong WJ,Simon MC.Hypoxia-inducible factors and the response to hypoxic stress[J]. Mol Cell,2010,40(2):294-309.
    [7] Xia Y,Choi HK,Lee K.Recent advances in hypoxia-inducible factor(HIF)-1 inhibitors[J]. Eur J Med Chem,2012,49:24-40.
    [8] Semenza GL.Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics[J]. Oncogene,2010,29(5):625-634.
    [9] Semenza GL.Targeting HIF-1 for cancer therapy[J]. Nat Rev Cancer,2003,3(10):721-732.
    [10] Semenza GL.Hypoxia-inducible factors in physiology and medicine[J]. Cell,2012,148(3):399-408.
    [11] Freedman SJ,Sun ZY,Poy F,et al.Structural basis for recruitment of CBP/p300 by hypoxia-inducible factor-1 alpha[J]. Proc Natl Acad Sci U S A,2002,99(8):5367-5372.
    [12] Shimoda LA, Semenza GL. Functional analysis of the role of hypoxia-inducible factor 1 in the pathogenesis of hypoxic pulmonary hypertension[J]. Methods Enzymol,2004,381(1):121-129.
    [13] Dames SA,Martinezyamout M,De Guzman RN,et al.Structural basis for Hif-1 alpha /CBP recognition in the cellular hypoxic response[J]. Proc Natl Acad Sci U S A,2002,99(8):5271-5276.
    [14] Kyle HF,Wickson KF,Stott J,et al.Exploration of the HIF-1α/p300 interface using peptide and Adhiron phage display technologies[J]. Mol Biosyst,2015,11(10):2738-2749.
    [15] Henchey LK, Kushal S, Dubey R, et al. Inhibition of hypoxia inducible factor 1 transcription coactivator interaction by a hydrogen bond surrogate α-helix[J]. J Am Chem Soc,2009,132(3):941-943.
    [16] Kushal S,Lao BB,Henchey LK,et al.Protein domain mimetics as in vivo modulators of hypoxia-inducible factor signaling[J]. Proc Natl Acad Sci U S A,2013,110(39):15602-15607.
    [17] Burslem GM,Kyle HF,Breeze AL,et al.Small-molecule proteomimetic inhibitors of the HIF-1α-p300 protein-protein Interaction[J]. ChemBioChem,2014,15(8):1083-1087
    [18] Lao BB, Grishagin I, Mesallati H, et al. In vivo modulation of hypoxia-inducible signaling by topographical helix mimetics[J]. Proc Natl Acad Sci U S A,2014,111(21):7531-7536.
    [19] Cook KM,Hilton ST,Mecinovi'c J,et al.Epidithiodiketopiperazines block the interaction between hypoxia-inducible factor-1α(HIF-1α)and p300 by a zinc ejection mechanism[J]. J Biol Chem,2009,284(39):26831-26838.
    [20] Block KM,Wang H,Szabo LZ,et al.Direct inhibition of hypoxia-inducible transcription factor complex with designed dimeric epidithiodiketopiperazine[J]. J Am Chem Soc,2009,131(50):18078-18088.
    [21] Reece KM,Richardson ED,Cook KM,et al.Epidithiodiketopiperazines(ETPs)exhibit in vitro antiangiogenic and in vivo antitumor activity by disrupting the HIF-1α/p300 complex in a preclinical model of prostate cancer[J]. Mol Cancer,2014,13(1):91.
    [22] Jayatunga MK,Thompson S,McKee TC,et al.Inhibition of the HIF1α-p300 interaction by quinone-and indandione-mediated ejection of structural Zn(II)[J]. Eur J Med Chem,2015, 94:509-516.
    [23] Na YR,Han KC,Park H,et al.Menadione and ethacrynic acid inhibit the hypoxia-inducible factor(HIF)pathway by disrupting HIF-1α interaction with p300[J]. Biochem Biophys Res Commun,2013,434(4):879-884.
    [24] Wu D,Zhang R,Zhao R,et al.A novel function of novobiocin:disrupting the interaction of HIF 1α and p300/CBP through direct binding to the HIF-1α C-terminal activation domain[J]. PLoS ONE,2013,8(5):e62014.
    [25] Kwon HS,Kim DR,Yang EG,et al.Inhibition of VEGF transcription through blockade of the hypoxia inducible factor-1α-p300 interaction by a small molecule[J]. Bioorg Med Chem Lett,2012,22(16):5249-5252.
    [26] Mooring SR,Jin H,Devi NS,et al.Design and synthesis of novel small-molecule inhibitors of the hypoxia inducible factor pathway[J]. J Med Chem,2011,54(24):8471-8489.
    [27] Mun J,Jabbar AA,Devi NS,et al.Design and in vitro activities of N-alkyl-N-[(8-R-2,2-dimethyl-2H-chromen-6-yl)methyl] heteroarylsulfonamides,novel,small-molecule hypoxia inducible factor-1 pathway inhibitors and anticancer agents[J]. J Med Chem,2012,55(15):6738-6750.
    [28] Shi Q,Yin S,Kaluz S,et al.Binding model for the interaction of anticancer arylsulfonamides with the p300 transcription cofactor[J]. ACS Med Chem Letters,2012,3(8):620-625.
    [29] Wang W,Ao L,Rayburn ER,et al.KCN1,a novel synthetic sulfonamide anticancer agent:in vitro and in vivo anti-pancreatic cancer activities and preclinical pharmacology[J]. PLoS ONE,2012,7(9):e44883.
    [30] Liu F,Sun HP,You QD.Advances in small-molecule inhibitor targeting Hsp 90-Cdc37 protein-protein interaction[J].J China Pharm Univ(中国药科大学学报),2015,46(3):272-278.
    • 相关文章
    • 施引文献
    • 资源附件(0)
计量
  • 文章访问数:  1163
  • HTML全文浏览量:  1
  • PDF下载量:  2676
  • 被引次数: 0
出版历程
  • 刊出日期:  2017-10-24

目录

摘要
HTML全文
    参考文献(30)
    相关文章
    施引文献
    资源附件(0)

    /

    返回文章
    返回

    版权所有：《中国药科大学学报》编辑部苏ICP备05007142号

    地址：江苏省南京市鼓楼区童家巷24号（210009）电话: 025-83271566E-mail: xuebao@cpu.edu.cn

    本系统由 北京仁和汇智信息技术有限公司 开发  百度统计

    访问量：454586

    x 关闭 永久关闭