The resurgence of covalent drugs

被引：1373

作者：

Singh, Juswinder ^{[1
]}

Petter, Russell C. ^{[1
]}

Baillie, Thomas A. ^{[2
]}

Whitty, Adrian ^{[3
]}

机构：

[1] Avila Therapeut, Waltham, MA 02453 USA

[2] Univ Washington, Sch Pharm, Seattle, WA 98195 USA

[3] Boston Univ, Metcalf Sci Ctr, Dept Chem, Boston, MA 02215 USA

来源：

NATURE REVIEWS DRUG DISCOVERY | 2011年 / 10卷 / 04期

关键词：

GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; IRREVERSIBLE INHIBITORS; METABOLIC-ACTIVATION; ABIRATERONE ACETATE; RESIDENCE TIME; EGF RECEPTOR; BINDING; DESIGN; FUTURE;

D O I：

10.1038/nrd3410

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：

Covalent drugs have proved to be successful therapies for various indications, but largely owing to safety concerns, they are rarely considered when initiating a target-directed drug discovery project. There is a need to reassess this important class of drugs, and to reconcile the discordance between the historic success of covalent drugs and the reluctance of most drug discovery teams to include them in their armamentarium. This Review surveys the prevalence and pharmacological advantages of covalent drugs, discusses how potential risks and challenges may be addressed through innovative design, and presents the broad opportunities provided by targeted covalent inhibitors.

引用

页码：307 / 317

页数：11

共 71 条

[1] Discovery and Characterization of a Highly Selective FAAH Inhibitor that Reduces Inflammatory Pain [J].

Ahn, Kay ;

Johnson, Douglas S. ;

Mileni, Mauro ;

Beidler, David ;

Long, Jonathan Z. ;

McKinney, Michele K. ;

Weerapana, Eranthie ;

Sadagopan, Nalini ;

Liimatta, Marya ;

Smith, Sarah E. ;

Lazerwith, Scott ;

Stiff, Cory ;

Kamtekar, Satwik ;

Bhattacharya, Keshab ;

Zhang, Yanhua ;

Swaney, Stephen ;

Van Becelaere, Keri ;

Stevens, Raymond C. ;

Cravatt, Benjamin F. .

CHEMISTRY & BIOLOGY, 2009, 16 (04) :411-420

[2] Future of toxicology-metabolic activation and drug design: Challenges and opportunities in chemical toxicology [J].

Baillie, Thomas A. .

CHEMICAL RESEARCH IN TOXICOLOGY, 2006, 19 (07) :889-893

[3]

Bartholow M., 2010, PHARM TIMES

[4] Neratinib, an Irreversible ErbB Receptor Tyrosine Kinase Inhibitor, in Patients With Advanced ErbB2-Positive Breast Cancer [J].

Burstein, Harold J. ;

Sun, Yan ;

Dirix, Luc Y. ;

Jiang, Zefei ;

Paridaens, Robert ;

Tan, Antoinette R. ;

Awada, Ahmad ;

Ranade, Anantbhushan ;

Jiao, Shunchang ;

Schwartz, Gary ;

Abbas, Richat ;

Powell, Christine ;

Turnbull, Kathleen ;

Vermette, Jennifer ;

Zacharchuk, Charles ;

Badwe, Rajendra .

JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (08) :1301-1307

[5] Inhibition of drug-resistant mutants of ABL, KIT, and EGF receptor kinases [J].

Carter, TA ;

Wodicka, LM ;

Shah, NP ;

Velasco, AM ;

Fabian, MA ;

Treiber, DK ;

Milanov, ZV ;

Atteridge, CE ;

Biggs, WH ;

Edeen, PT ;

Floyd, M ;

Ford, JM ;

Grotzfeld, RM ;

Herrgard, S ;

Insko, DE ;

Mehta, SA ;

Patel, HK ;

Pao, W ;

Sawyers, CL ;

Varmus, H ;

Zarrinkar, PP ;

Lockhart, DJ .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (31) :11011-11016

[6]

Chandrasekaran Appavu, 2010, Drug Metab Lett, V4, P220

[7]

Choi S, 2010, NAT CHEM BIOL, V6, P133, DOI [10.1038/NCHEMBIO.281, 10.1038/nchembio.281]

[8] Structural bioinformatics-based design of selective, irreversible kinase inhibitors [J].

Cohen, MS ;

Zhang, C ;

Shokat, KM ;

Taunton, J .

SCIENCE, 2005, 308 (5726) :1318-1321

[9]

Copeland RA, 2013, EVALUATION OF ENZYME INHIBITORS IN DRUG DISCOVERY: A GUIDE FOR MEDICINAL CHEMISTS AND PHARMACOLOGISTS, 2ND EDITION, P1, DOI 10.1002/9781118540398

[10] Opinion - Drug-target residence time and its implications for lead optimization [J].

Copeland, Robert A. ;

Pompliano, David L. ;

Meek, Thomas D. .

NATURE REVIEWS DRUG DISCOVERY, 2006, 5 (09) :730-739

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