Place your BETs: the therapeutic potential of bromodomains

被引：174

作者：

Prinjha, R. K. ^{[1
]}

Witherington, J. ^{[1
]}

Lee, K. ^{[1
]}

机构：

[1] GlaxoSmithKline PLC, Med Res Ctr, Immunoinflammat Ctr Excellence Drug Discovery, Epinova DPU, Stevenage SG1 2NY, Herts, England

来源：

TRENDS IN PHARMACOLOGICAL SCIENCES | 2012年 / 33卷 / 03期

关键词：

CHROMATIN-REMODELING COMPLEX; BIPOLAR AFFECTIVE-DISORDER; PAPILLOMAVIRUS E2 PROTEIN; HOST MITOTIC CHROMOSOMES; NUCLEAR-BODY; BAF COMPLEX; HISTONE MODIFICATIONS; SUSCEPTIBILITY LOCI; STRUCTURAL BASIS; GENE-EXPRESSION;

D O I：

10.1016/j.tips.2011.12.002

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Therapeutic targeting of the processes that regulate histone modification is a growing area of scientific exploration. Although most interest has concentrated on the various families of enzymes that contribute to these processes, this review focuses on emerging data demonstrating the chemical tractability and therapeutic potential of a hitherto underexplored family of proteins, namely the bromodomain (BRD) family of reader proteins. These proteins perform a crucial role in translating histone modifications with powerful transcriptional consequences. We review current knowledge of the biology of this emergent target class and highlight recent breakthroughs that now make the BRD family of reader proteins attractive for drug discovery.

引用

页码：146 / 153

页数：8

共 82 条

[11] The multi-tasking P-TEFb complex [J].

Bres, Vanessa ;

Yoh, Sunnie M. ;

Jones, Katherine A. .

CURRENT OPINION IN CELL BIOLOGY, 2008, 20 (03) :334-340

[12] Functional characterization of ATAD2 as a new cancer/testis factor and a predictor of poor prognosis in breast and lung cancers [J].

Caron, C. ;

Lestrat, C. ;

Marsal, S. ;

Escoffier, E. ;

Curtet, S. ;

Virolle, V. ;

Barbry, P. ;

Debernardi, A. ;

Brambilla, C. ;

Brambilla, E. ;

Rousseaux, S. ;

Khochbin, S. .

ONCOGENE, 2010, 29 (37) :5171-5181

[13] Isolation and functional characterization of P-TEFb-associated factors that control general and HIV-1 transcriptional elongation [J].

Chen, Ruichuan ;

Liu, Min ;

Zhang, Kai ;

Zhou, Qiang .

METHODS, 2011, 53 (01) :85-90

[14] A BAF-centred view of the immune system [J].

Chi, T .

NATURE REVIEWS IMMUNOLOGY, 2004, 4 (12) :965-977

[15]

CHISSOE S, 2008, United States Patent Application Publication, Patent No. [US 2008/0108077 A1, 20080108077, US2008/0108077]

[16] Discovery and Characterizatlion of Small Molecule Inhibitors of the BET Family Bromodomains [J].

Chung, Chun-wa ;

Coste, Herve ;

White, Julia H. ;

Mirguet, Olivier ;

Wilde, Jonathan ;

Gosmini, Romain L. ;

Delves, Chris ;

Magny, Sylvie M. ;

Woodward, Robert ;

Hughes, Stephen A. ;

Boursier, Eric V. ;

Flynn, Helen ;

Bouillot, Anne M. ;

Bamborough, Paul ;

Brusq, Jean-Marie G. ;

Gellibert, Francoise J. ;

Jones, Emma J. ;

Riou, Alizon M. ;

Homes, Paul ;

Martin, Sandrine L. ;

Uings, Iain J. ;

Toum, Jerome ;

Clement, Catherine A. ;

Boullay, Anne-Benedicte ;

Grimley, Rachel L. ;

Blande, Florence M. ;

Prinjha, Rab K. ;

Lee, Kevin ;

Kirilovsky, Jorge ;

Nicodeme, Edwige .

JOURNAL OF MEDICINAL CHEMISTRY, 2011, 54 (11) :3827-3838

[17] ATAD2 Is a Novel Cofactor for MYC, Overexpressed and Amplified in Aggressive Tumors [J].

Ciro, Marco ;

Prosperini, Elena ;

Quarto, Micaela ;

Grazini, Ursula ;

Walfridsson, Julian ;

McBlane, Fraser ;

Nucifero, Paolo ;

Pacchiana, Giovanni ;

Capra, Maria ;

Christensen, Jesper ;

Helin, Kristian .

CANCER RESEARCH, 2009, 69 (21) :8491-8498

[18] The immunopathogenesis of sepsis [J].

Cohen, J .

NATURE, 2002, 420 (6917) :885-891

[19] Bromodomain 4 activation predicts breast cancer survival [J].

Crawford, Nigel P. S. ;

Alsarraj, Jude ;

Lukes, Luanne ;

Walker, Renard C. ;

Officewala, Jennifer S. ;

Yang, Howard H. ;

Lee, Maxwell P. ;

Ozato, Keiko ;

Hunter, Kent W. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (17) :6380-6385

[20] The chromatin-remodeling BAF complex mediates cellular antiviral activities by promoter priming [J].

Cui, KR ;

Tailor, P ;

Liu, H ;

Chen, X ;

Ozato, K ;

Zhao, K .

MOLECULAR AND CELLULAR BIOLOGY, 2004, 24 (10) :4476-4486

← 1 2 3 4 5 6 7 8 9 →