Biased and unbiased strategies to identify biologically active small molecules

被引：14

作者：

Abet, Valentina ^{[1
]}

Mariani, Angelica ^{[1
]}

Truscott, Fiona R. ^{[1
]}

Britton, Sebastien ^{[2
,3
]}

Rodriguez, Raphael ^{[1
]}

机构：

[1] CNRS, Inst Chim Subst Nat, Ctr Rech Gif, F-91198 Gif Sur Yvette, France

[2] CNRS, Inst Pharmacol & Biol Struct, F-31077 Toulouse, France

[3] Univ Toulouse 3, Univ Toulouse, Equipe Labellisee Ligue Canc, F-31077 Toulouse, France

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2014年 / 22卷 / 16期

关键词：

Drug discovery; Dynamic combinatorial chemistry; In situ click chemistry; Fragment-based drug discovery; Diversity-oriented synthesis; DIVERSITY-ORIENTED SYNTHESIS; SITU CLICK CHEMISTRY; DYNAMIC COMBINATORIAL CHEMISTRY; DEPENDENT KINASE INHIBITOR; FRAGMENT-BASED DISCOVERY; HISTONE DEACETYLASE INHIBITORS; POTENT AURORA KINASE; CELL-BASED ASSAYS; DRUG DISCOVERY; IN-SITU;

D O I：

10.1016/j.bmc.2014.04.019

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Small molecules are central players in chemical biology studies. They promote the perturbation of cellular processes underlying diseases and enable the identification of biological targets that can be validated for therapeutic intervention. Small molecules have been shown to accurately tune a single function of pluripotent proteins in a reversible manner with exceptional temporal resolution. The identification of molecular probes and drugs remains a worthy challenge that can be addressed by the use of biased and unbiased strategies. Hypothesis-driven methodologies employs a known biological target to synthesize complementary hits while discovery-driven strategies offer the additional means of identifying previously unanticipated biological targets. This review article provides a general overview of recent synthetic frameworks that gave rise to an impressive arsenal of biologically active small molecules with unprecedented cellular mechanisms. (C) 2014 Published by Elsevier Ltd.

引用

页码：4474 / 4489

页数：16

共 118 条

[11] Combining Hit Identification Strategies: Fragment-Based and in Silico Approaches to Orally Active 2-Aminothieno[2,3-d]pyrimidine Inhibitors of the Hsp90 Molecular Chaperone [J].

Brough, Paul A. ;

Barril, Xavier ;

Borgognoni, Jenifer ;

Chene, Patrick ;

Davies, Nicholas G. M. ;

Davis, Ben ;

Drysdale, Martin J. ;

Dymock, Brian ;

Eccles, Suzanne A. ;

Garcia-Echeverria, Carlos ;

Fromont, Christophe ;

Hayes, Angela ;

Hubbard, Roderick E. ;

Jordan, Allan M. ;

Jensen, Michael Rugaard ;

Massey, Andrew ;

Merrett, Angela ;

Padfield, Antony ;

Parsons, Rachel ;

Radimerski, Thomas ;

Raynaud, Florence I. ;

Robertson, Alan ;

Roughley, Stephen D. ;

Schoepfer, Joseph ;

Simmonite, Heather ;

Sharp, Swee Y. ;

Surgenor, Allan ;

Valenti, Melanie ;

Walls, Steven ;

Webb, Paul ;

Wood, Mike ;

Workman, Paul ;

Wright, Lisa .

JOURNAL OF MEDICINAL CHEMISTRY, 2009, 52 (15) :4794-4809

[12]

Bunyapaiboonsri T, 2001, CHEMBIOCHEM, V2, P438

[13] A planning strategy for diversity-oriented synthesis [J].

Burke, MD ;

Schreiber, SL .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2004, 43 (01) :46-58

[14] Discovery of an Aurora kinase inhibitor through site-specific dynamic combinatorial chemistry [J].

Cancilla, Mark T. ;

He, Molly M. ;

Viswanathan, Nina ;

Simmons, Robert L. ;

Taylor, Meggin ;

Fung, Amy D. ;

Cao, Kathy ;

Erlanson, Daniel A. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2008, 18 (14) :3978-3981

[15] Fragment-based lead discovery: leads by design [J].

Carr, RAE ;

Congreve, M ;

Murray, CW ;

Rees, DC .

DRUG DISCOVERY TODAY, 2005, 10 (14) :987-992

[16] Improved Survival with Vemurafenib in Melanoma with BRAF V600E Mutation [J].

Chapman, Paul B. ;

Hauschild, Axel ;

Robert, Caroline ;

Haanen, John B. ;

Ascierto, Paolo ;

Larkin, James ;

Dummer, Reinhard ;

Garbe, Claus ;

Testori, Alessandro ;

Maio, Michele ;

Hogg, David ;

Lorigan, Paul ;

Lebbe, Celeste ;

Jouary, Thomas ;

Schadendorf, Dirk ;

Ribas, Antoni ;

O'Day, Steven J. ;

Sosman, Jeffrey A. ;

Kirkwood, John M. ;

Eggermont, Alexander M. M. ;

Dreno, Brigitte ;

Nolop, Keith ;

Li, Jiang ;

Nelson, Betty ;

Hou, Jeannie ;

Lee, Richard J. ;

Flaherty, Keith T. ;

McArthur, Grant A. .

NEW ENGLAND JOURNAL OF MEDICINE, 2011, 364 (26) :2507-2516

[17] Lessons for fragment library design: analysis of output from multiple screening campaigns [J].

Chen, I-Jen ;

Hubbard, Roderick E. .

JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN, 2009, 23 (08) :603-620

[18] Probing riboswitch-ligand interactions using thiamine pyrophosphate analogues [J].

Chen, Liuhong ;

Cressina, Elena ;

Dixon, Neil ;

Erixon, Karl ;

Agyei-Owusu, Kwasi ;

Micklefield, Jason ;

Smith, Alison G. ;

Abell, Chris ;

Leeper, Finian J. .

ORGANIC & BIOMOLECULAR CHEMISTRY, 2012, 10 (30) :5924-5931

[19] A Fragment-Based Approach to Identifying Ligands for Riboswitches [J].

Chen, Liuhong ;

Cressina, Elena ;

Leeper, Finian J. ;

Smith, Alison G. ;

Abell, Chris .

ACS CHEMICAL BIOLOGY, 2010, 5 (04) :355-358

[20] Synthesis of a Novel Suppressor of β-Cell Apoptosis via Diversity-Oriented Synthesis [J].

Chou, Danny Hung-Chieh ;

Duvall, Jeremy R. ;

Gerard, Baudouin ;

Liu, Haibo ;

Pandya, Bhaumik A. ;

Suh, Byung-Chul ;

Forbeck, Erin M. ;

Faloon, Patrick ;

Wagner, Bridget K. ;

Marcaurelle, Lisa A. .

ACS MEDICINAL CHEMISTRY LETTERS, 2011, 2 (09) :698-702

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