Adaptation of High-Throughput Screening in Drug Discovery-Toxicological Screening Tests

被引:197
|
作者
Szymanski, Pawel [1 ]
Markowicz, Magdalena [1 ]
Mikiciuk-Olasik, Elzbieta [1 ]
机构
[1] Med Univ Lodz, Dept Pharmaceut Chem & Drug Anal, PL-90151 Lodz, Poland
来源
关键词
High-throughput screening (HTS); cellular microarrays; drug development; toxicity; PROLIFERATOR-ACTIVATED RECEPTOR; MASS-SPECTROMETRY; CELL-LINES; SALMONELLA MUTAGENICITY; COMBINATORIAL LIBRARIES; PHARMACEUTICAL ANALYSIS; RODENT CARCINOGENICITY; HEPATIC-CLEARANCE; CHEMICAL TOXICITY; HUMAN HEPATOCYTES;
D O I
10.3390/ijms13010427
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
High-throughput screening (HTS) is one of the newest techniques used in drug design and may be applied in biological and chemical sciences. This method, due to utilization of robots, detectors and software that regulate the whole process, enables a series of analyses of chemical compounds to be conducted in a short time and the affinity of biological structures which is often related to toxicity to be defined. Since 2008 we have implemented the automation of this technique and as a consequence, the possibility to examine 100,000 compounds per day. The HTS method is more frequently utilized in conjunction with analytical techniques such as NMR or coupled methods e. g., LC-MS/MS. Series of studies enable the establishment of the rate of affinity for targets or the level of toxicity. Moreover, researches are conducted concerning conjugation of nanoparticles with drugs and the determination of the toxicity of such structures. For these purposes there are frequently used cell lines. Due to the miniaturization of all systems, it is possible to examine the compound's toxicity having only 1-3 mg of this compound. Determination of cytotoxicity in this way leads to a significant decrease in the expenditure and to a reduction in the length of the study.
引用
收藏
页码:427 / 452
页数:26
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