The beautiful cell: high-content screening in drug discovery

被引：122

作者：

Bickle, Marc ^{[1
]}

机构：

[1] Max Planck Inst Mol Cell Biol & Genet, Technol Dev Studio, D-01307 Dresden, Germany

来源：

ANALYTICAL AND BIOANALYTICAL CHEMISTRY | 2010年 / 398卷 / 01期

关键词：

High-content screening; Imaging; Drug discovery; Multiparametric; Cell-based assay; IN-VITRO; IMAGE-ANALYSIS; CHEMICAL-MODIFICATION; IDENTIFICATION; GENOME; MICROSCOPY; ASSAY; DIFFERENTIATION; CYTOTOXICITY; HEPATOTOXICITY;

D O I：

10.1007/s00216-010-3788-3

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

The term "high-content screening" has become synonymous with imaging screens using automated microscopes and automated image analysis. The term was coined a little over 10 years ago. Since then the technology has evolved considerably and has established itself firmly in the drug discovery and development industry. Both the instruments and the software controlling the instruments and analyzing the data have come to maturity, so the full benefits of high-content screening can now be realized. Those benefits are the capability of carrying out phenotypic multiparametric cellular assays in an unbiased, fully automated, and quantitative fashion. Automated microscopes and automated image analysis are being applied at all stages of the drug discovery and development pipeline. All major pharmaceutical companies have adopted the technology and it is in the process of being embraced broadly by the academic community. This review aims at describing the current capabilities and limits of the technology as well as highlighting necessary developments that are required to exploit fully the potential of high-content screening and analysis.

引用

页码：219 / 226

页数：8

共 70 条

[1] Application of a high-content multiparameter cytotoxicity assay to prioritize compounds based on toxicity potential in humans [J].

Abraham, Vivek C. ;

Towne, Danli L. ;

Waring, Jeffrey E. ;

Warrior, Usha ;

Burns, David J. .

JOURNAL OF BIOMOLECULAR SCREENING, 2008, 13 (06) :527-537

[2] SPENDING ON NEW DRUG DEVELOPMENT [J].

Adams, Christopher Paul ;

Brantner, Van Vu .

HEALTH ECONOMICS, 2010, 19 (02) :130-141

[3] Nuclear export inhibitors and kinase inhibitors identified using a MAPK-activated protein kinase 2 Redistribution® screen [J].

Almholt, DLC ;

Loechel, F ;

Nielsen, SJ ;

Krog-Jensen, C ;

Terry, R ;

Bjorn, SP ;

Pedersen, HC ;

Præstegaard, M ;

Moller, S ;

Heide, M ;

Pagliaro, L ;

Mason, AJ ;

Butcher, S ;

Dahl, SW .

ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES, 2004, 2 (01) :7-20

[4] The use of high-content screening for the discovery and characterization of compounds that modulate mitotic index and cell cycle progression by differing mechanisms of action [J].

Barabasz, Amy ;

Foley, Briana ;

Otto, James C. ;

Scott, Anisa ;

Rice, John .

ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES, 2006, 4 (02) :153-163

[5] DNA Methylation Analysis as a Tool for Cell Typing [J].

Baron, Udo ;

Tuerbachova, Ivana ;

Hellwag, Alexander ;

Eckhardt, Florian ;

Berlin, Kurt ;

Hoffmuller, Ulrich ;

Gardina, Paul ;

Olek, Sven .

EPIGENETICS, 2006, 1 (01) :55-60

[6] Cellular image analysis and imaging by flow cytometry [J].

Basiji, David A. ;

Ortyn, William E. ;

Liang, Luchuan ;

Venkatachalam, Vidya ;

Morrissey, Philip .

CLINICS IN LABORATORY MEDICINE, 2007, 27 (03) :653-+

[7] High-throughput phagocytosis assay utilizing a pH-sensitive fluorescent dye [J].

Beletskii, A ;

Cooper, M ;

Sriraman, P ;

Chiriac, C ;

Zhao, LH ;

Abbot, S ;

Yu, LM .

BIOTECHNIQUES, 2005, 39 (06) :894-897

[8] Identification and characterization of cholest-4-en-3-one, oxime (TRO19622), a novel drug candidate for amyotrophic lateral sclerosis [J].

Bordet, Thierry ;

Buisson, Bruno ;

Michaud, Magali ;

Drouot, Cyrille ;

Galea, Pascale ;

Delaage, Pierre ;

Akentieva, Natalia P. ;

Evers, Alex S. ;

Covey, Douglas F. ;

Ostuni, Mariano A. ;

Lacapere, Jean-Jacques ;

Massaad, Charbel ;

Schumacher, Michael ;

Steidl, Esther-Marie ;

Maux, Delphine ;

Delaage, Michel ;

Henderson, Christopher E. ;

Pruss, Rebecca M. .

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2007, 322 (02) :709-720

[9] A large-scale chemical modification screen identifies design rules to generate siRNAs with high activity, high stability and low toxicity [J].

Bramsen, Jesper B. ;

Laursen, Maria B. ;

Nielsen, Anne F. ;

Hansen, Thomas B. ;

Bus, Claus ;

Langkjaer, Niels ;

Babu, B. Ravindra ;

Hojland, Torben ;

Abramov, Mikhail ;

Van Aerschot, Arthur ;

Odadzic, Dalibor ;

Smicius, Romualdas ;

Haas, Jens ;

Andree, Cordula ;

Barman, Jharna ;

Wenska, Malgorzata ;

Srivastava, Puneet ;

Zhou, Chuanzheng ;

Honcharenko, Dmytro ;

Hess, Simone ;

Mueller, Elke ;

Bobkov, Georgii V. ;

Mikhailov, Sergey N. ;

Fava, Eugenio ;

Meyer, Thomas F. ;

Chattopadhyaya, Jyoti ;

Zerial, Marino ;

Engels, Joachim W. ;

Herdewijn, Piet ;

Wengel, Jesper ;

Kjems, Jorgen .

NUCLEIC ACIDS RESEARCH, 2009, 37 (09) :2867-2881

[10]

BRENNER S, 1974, GENETICS, V77, P71

← 1 2 3 4 5 6 7 →