High-Throughput Screening Methods in Drug Discovery

Advanced methods of combinatory chemistry have made it possible to quickly synthesize vast quantities of compounds for testing. These compounds are then tested in a rapid method of evaluation called high-throughput screening. High-throughput screening (HTS) allows researchers to  quickly and cost-effectively process thousands and even hundreds of thousands (ultra-high-throughput screening, or uHTS) of compounds, which in turn enables them to zero in on hits (compounds that display the desired characteristic) to be advanced into the next stages of drug discovery and development.

HTS is used in identifying target-specific compounds, and can also be used to characterize pharmacokinetic (PK) and pharmacodynamic (PD) data of compounds. HTS methods are a great asset to the drug discovery process, providing researchers an excellent starting point as well as saving them time and money.

High-throughput screening incorporates complex automation systems, including multiple operating systems, computers, specialized software, and robotic grippers that are used to automatically process microplates through each step of a prescribed assay. Assay microplates are comprised of a large number of wells (384, 1,536, or 3,456 wells per plate), and samples from a stock plate within a compound library are applied to each well.

Chemical compounds are added to each well, in a manner that depends on the design and purpose of the assay. A number of fluorescence-based detection methods may be used, depending on the target and nature of the investigation. Positive results of a primary screen are considered “hits,” and are taken into secondary screening for further quantification.

Successful high-throughput screening relies on many factors including; target selection, selection of the library to be screened, assay design, software and hardware design, effective statistical analysis, and data management. Highly sensitive fluorescence-based detection techniques are beneficial as an increased density of microplates (up to 3,456 wells per plate) is coupled with a drastic decrease in the amount of a sample that is required for an assay. This decrease in sample volume required and the speed and precision in automation and careful planning allows for a much more efficient use of resources, while speeding the discovery and development process along.

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Categories: Toxicology and Pharmacology

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