The use of immortalized cell lines in GPCR screening: the good, bad and ugly.

Eglen RM; Gilchrist A; Reisine T

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The use of immortalized cell lines in GPCR screening: the good, bad and ugly.

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For most membrane-bound molecular targets, including G protein linked receptors (GPCRs), the optimal approach in drug discovery involves the use of cell based high throughput screening (HTS) technologies to identify compounds that modulate target activity. Most GPCRs have been cloned and can therefore be routinely expressed in immortalized cell lines. These cells can be easily and rapidly grown in unlimited quantities making them ideal for use in current HTS technologies. A significant advantage of this approach is that immortalized recombinant cells provide a homogenous background for expression of the target which greatly facilitates consistency in screening, thus allowing for a better understanding of the mechanism of action of the interacting compound or drug. Nonetheless, it is now evident that numerous disparities exist between the physiological environment of screening systems using recombinant cells and natural tissues. This has lead to a problem in the validity of the pharmacological data obtained using immortalized cells in as much as such cells do not always reflect the desired clinical efficacy and safety of the compounds under examination. This brief review discusses these issues and describes how they influence the discovery of drugs using modern HTS.

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《Combinatorial chemistry & high throughput screening》 |2008年第7期|560-565|共6页
作者
Eglen RM; Gilchrist A; Reisine T;
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作者单位

Bio-Discovery, PerkinElmer Life and Analytical Sciences, Waltham, MA 02451-1457, USA. richard.eglen@perkinelmer.com;

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原文格式 PDF
正文语种英语
中图分类化学;
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Aspects of disease screening; immortalized cell; pharmacological; drug discovery;

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The use of immortalized cell lines in GPCR screening: the good, bad and ugly.

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