Chromatin proteins and modifications as drug targets

被引：330
作者：
Helin, Kristian [1 ,2 ,3 ]
Dhanak, Dashyant [4 ]
机构：
[1] Univ Copenhagen, Biotech Res & Innovat Ctr, DK-2200 Copenhagen, Denmark
[2] Univ Copenhagen, Ctr Epigenet, DK-2200 Copenhagen, Denmark
[3] Univ Copenhagen, Danish Stem Cell Ctr, DK-2200 Copenhagen, Denmark
[4] Janssen Res & Dev, Spring House, PA 19477 USA
来源：
NATURE | 2013年 / 502卷 / 7472期
基金：
欧洲研究理事会; 新加坡国家研究基金会;
关键词：
HISTONE METHYLTRANSFERASE EZH2; SMALL-MOLECULE INHIBITOR; THERAPEUTIC STRATEGY; SOMATIC MUTATIONS; CHEMICAL PROBE; SELECTIVE-INHIBITION; DEMETHYLASE GENE; HDAC INHIBITORS; CANCER-CELLS; LYSINE; 27;
D O I：
10.1038/nature12751
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
A plethora of groundbreaking studies have demonstrated the importance of chromatin-associated proteins and post-translational modifications of histones, proteins and DNA (so-called epigenetic modifications) for transcriptional control and normal development. Disruption of epigenetic control is a frequent event in disease, and the first epigenetic-based therapies for cancer treatment have been approved. A generation of new classes of potent and specific inhibitors for several chromatin-associated proteins have shown promise in preclinical trials. Although the biology of epigenetic regulation is complex, new inhibitors such as these will hopefully be of clinical use in the coming years.
引用
收藏
页码：480 / 488
页数：9
相关论文
共 103 条
  • [1] N-Benzyl-1-heteroaryl-3-(trifluoromethyl)-1H-pyrazole-5-carboxamides as inhibitors of co-activator associated arginine methyltransferase 1 (CARM1)
    Allan, Martin
    Manku, Sukhdev
    Therrien, Eric
    Nguyen, Natalie
    Styhler, Sylvia
    Robert, Marie-France
    Goulet, Anne-Christine
    Petschner, Andrea J.
    Rahil, Gabi
    MacLeod, A. Robert
    Deziel, Robert
    Besterman, Jeffrey M.
    Nguyen, Hannah
    Wahhab, Amal
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2009, 19 (04) : 1218 - 1223
  • [2] Three-dimensional culture sensitizes epithelial ovarian cancer cells to EZH2 methyltransferase inhibition
    Amatangelo, Michael D.
    Garipov, Azat
    Li, Hua
    Conejo-Garcia, Jose R.
    Speicher, David W.
    Zhang, Rugang
    [J]. CELL CYCLE, 2013, 12 (13) : 2113 - 2119
  • [3] Synthesis and Structure-Activity Relationship Investigation of Adenosine-Containing Inhibitors of Histone Methyltransferase DOT1L
    Anglin, Justin L.
    Deng, Lisheng
    Yao, Yuan
    Cai, Guobin
    Liu, Zhen
    Jiang, Hong
    Cheng, Gang
    Chen, Pinhong
    Dong, Shuo
    Song, Yongcheng
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2012, 55 (18) : 8066 - 8074
  • [4] A decade of exploring the cancer epigenome - biological and translational implications
    Baylin, Stephen B.
    Jones, Peter A.
    [J]. NATURE REVIEWS CANCER, 2011, 11 (10) : 726 - 734
  • [5] EZH2 Is Required for Germinal Center Formation and Somatic EZH2 Mutations Promote Lymphoid Transformation
    Beguelin, Wendy
    Popovic, Relja
    Teater, Matt
    Jiang, Yanwen
    Bunting, Karen L.
    Rosen, Monica
    Shen, Hao
    Yang, Shao Ning
    Wang, Ling
    Ezponda, Teresa
    Martinez-Garcia, Eva
    Zhang, Haikuo
    Zheng, Yupeng
    Verma, Sharad K.
    McCabe, Michael T.
    Ott, Heidi M.
    Van Aller, Glenn S.
    Kruger, Ryan G.
    Liu, Yan
    McHugh, Charles F.
    Scott, David W.
    Chung, Young Rock
    Kelleher, Neil
    Shaknovich, Rita
    Creasy, Caretha L.
    Gascoyne, Randy D.
    Wong, Kwok-Kin
    Cerchietti, Leandro
    Levine, Ross L.
    Abdel-Wahab, Omar
    Licht, Jonathan D.
    Elemento, Olivier
    Melnick, Ari M.
    [J]. CANCER CELL, 2013, 23 (05) : 677 - 692
  • [6] The complex language of chromatin regulation during transcription
    Berger, Shelley L.
    [J]. NATURE, 2007, 447 (7143) : 407 - 412
  • [7] MLL-Rearranged Leukemia Is Dependent on Aberrant H3K79 Methylation by DOT1L
    Bernt, Kathrin M.
    Zhu, Nan
    Sinha, Amit U.
    Vempati, Sridhar
    Faber, Joerg
    Krivtsov, Andrei V.
    Feng, Zhaohui
    Punt, Natalie
    Daigle, Amanda
    Bullinger, Lars
    Pollock, Roy M.
    Richon, Victoria M.
    Kung, Andrew L.
    Armstrong, Scott A.
    [J]. CANCER CELL, 2011, 20 (01) : 66 - 78
  • [8] EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer
    Adrian P. Bracken
    Diego Pasini
    Maria Capra
    Elena Prosperini
    Elena Colli
    Kristian Helin
    [J]. The EMBO Journal, 2003, 22 (20) : 5323 - 5335
  • [9] Copeland R. A., 2012, PCT Int. Appl. Pat., Patent No. [WO 2012034132, 2012034132]
  • [10] Daigle S. R., 2013, BLOOD
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