Deubiquitylating enzymes and drug discovery: emerging opportunities

被引：545

作者：

Harrigan, Jeanine A. ^{[1
]}

Jacq, Xavier ^{[1
]}

Martin, Niall M. ^{[1
,2
]}

Jackson, Stephen P. ^{[1
,3
,4
,5
]}

机构：

[1] Mission Therapeut Ltd, Babraham Res Campus, Cambridge CB22 3AT, England

[2] Artios Pharmaceut Ltd, Babraham Res Campus, Cambridge CB22 3AT, England

[3] Univ Cambridge, Wellcome Trust, Tennis Court Rd, Cambridge CB2 1QN, England

[4] Univ Cambridge, Canc Res UK Gurdon Inst, Tennis Court Rd, Cambridge CB2 1QN, England

[5] Univ Cambridge, Dept Biochem, Tennis Court Rd, Cambridge CB2 1QN, England

来源：

NATURE REVIEWS DRUG DISCOVERY | 2018年 / 17卷 / 01期

基金：

英国惠康基金;

关键词：

NF-KAPPA-B; UBIQUITIN-SPECIFIC PROTEASE; SMALL-MOLECULE INHIBITOR; GERMLINE BAP1 MUTATIONS; DNA-DAMAGE RESPONSE; C-TERMINAL HYDROLASE-L1; ANEURYSMAL BONE-CYST; PAPAIN-LIKE PROTEASE; PEPTIDASE; 11; USP11; GENE-PRODUCT; 9.5;

D O I：

10.1038/nrd.2017.152

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

More than a decade after a Nobel Prize was awarded for the discovery of the ubiquitin-proteasome system and clinical approval of proteasome and ubiquitin E3 ligase inhibitors, first-generation deubiquitylating enzyme (DUB) inhibitors are now approaching clinical trials. However, although our knowledge of the physiological and pathophysiological roles of DUBs has evolved tremendously, the clinical development of selective DUB inhibitors has been challenging. In this Review, we discuss these issues and highlight recent advances in our understanding of DUB enzymology and biology as well as technological improvements that have contributed to the current interest in DUBs as therapeutic targets in diseases ranging from oncology to neurodegeneration.

引用

页码：57 / 77

页数：21

共 302 条

[21] A novel active site-directed probe specific for deubiquitylating enzymes reveals proteasome association of USP14 [J].

Borodovsky, A ;

Kessler, BM ;

Casagrande, R ;

Overkleeft, HS ;

Wilkinson, KD ;

Ploegh, HL .

EMBO JOURNAL, 2001, 20 (18) :5187-5196

[22] Expression of the deubiquitinating enzyme mUBPy in the mouse brain [J].

Bruzzone, Federica ;

Vallarino, Mauro ;

Berruti, Giovanna ;

Angelini, Cristiano .

BRAIN RESEARCH, 2008, 1195 :56-66

[23] Mitoxantrone Targets Human Ubiquitin-Specific Peptidase 11 (USP11) and Is a Potent Inhibitor of Pancreatic Cancer Cell Survival [J].

Burkhart, Richard A. ;

Peng, Yu ;

Norris, Zoe A. ;

Tholey, Renee M. ;

Talbott, Vanessa A. ;

Liang, Qin ;

Ai, Yongxing ;

Miller, Kathy ;

Lal, Shruti ;

Cozzitorto, Joseph A. ;

Witkiewicz, Agnieska K. ;

Yeo, Charles J. ;

Gehrmann, Matthew ;

Napper, Andrew ;

Winter, Jordan M. ;

Sawicki, Janet A. ;

Zhuang, Zhihao ;

Brody, Jonathan R. .

MOLECULAR CANCER RESEARCH, 2013, 11 (08) :901-911

[24] USP8 Is a Novel Target for Overcoming Gefitinib Resistance in Lung Cancer [J].

Byun, Sanguine ;

Lee, Sung-Young ;

Lee, Jihoon ;

Jeong, Chul-Ho ;

Farrand, Lee ;

Lim, Semi ;

Reddy, Kanamata ;

Kim, Ji Young ;

Lee, Mee-Hyun ;

Lee, Hyong Joo ;

Bode, Ann M. ;

Lee, Ki Won ;

Dong, Zigang .

CLINICAL CANCER RESEARCH, 2013, 19 (14) :3894-3904

[25] FANCI Regulates Recruitment of the FA Core Complex at Sites of DNA Damage Independently of FANCD2 [J].

Castella, Maria ;

Jacquemont, Celine ;

Thompson, Elizabeth L. ;

Yeo, Jung Eun ;

Cheung, Ronald S. ;

Huang, Jen-Wei ;

Sobeck, Alexandra ;

Hendrickson, Eric A. ;

Taniguchi, Toshiyasu .

PLoS Genetics, 2015, 11 (10)

[26] A20 in inflammation and autoimmunity [J].

Catrysse, Leen ;

Vereecke, Lars ;

Beyaert, Rudi ;

van Loo, Geert .

TRENDS IN IMMUNOLOGY, 2014, 35 (01) :22-31

[27] The deubiquitinating enzyme UBPy/USP8 interacts with TrkA and inhibits neuronal differentiation in PC12 cells [J].

Ceriani, Michela ;

Amigoni, Loredana ;

D'Aloia, Alessia ;

Berruti, Giovanna ;

Martegani, Enzo .

EXPERIMENTAL CELL RESEARCH, 2015, 333 (01) :49-59

[28]

Chambers R. J., 2013, Patent No. [WO 2013112699, 2013112699]

[29]

Chambers R. J., 2013, Patent No. [WO 2013112651, 2013112651]

[30] A Small Molecule Inhibitor of Ubiquitin-Specific Protease-7 Induces Apoptosis in Multiple Myeloma Cells and Overcomes Bortezomib Resistance [J].

Chauhan, Dharminder ;

Tian, Ze ;

Nicholson, Benjamin ;

Kumar, K. G. Suresh ;

Zhou, Bin ;

Carrasco, Ruben ;

McDermott, Jeffrey L. ;

Leach, Craig A. ;

Fulcinniti, Mariaterresa ;

Kodrasov, Matthew P. ;

Weinstock, Joseph ;

Kingsbury, William D. ;

Hideshima, Teru ;

Shah, Parantu K. ;

Minvielle, Stephane ;

Altun, Mikael ;

Kessler, Benedikt M. ;

Orlowski, Robert ;

Richardson, Paul ;

Munshi, Nikhil ;

Anderson, Kenneth C. .

CANCER CELL, 2012, 22 (03) :345-358

← 1 2 3 4 5 6 7 8 9 10 →