High-Throughput Screening: The Hits and Leads of Drug Discovery- An Overview

The mechanism-based approach which corresponds to the target-based approach screens for compounds with a specific mode of action. The highly effective nature of high-throughput screening (HTS) for identification of highly target specific compounds is attributed to its precise focus on single mechanism. This logical development of receptor technology is closely connected with the changes in strategy of chemical synthesis. The vast number of compounds produced by combinatorial chemistry and the possibility of testing many compounds, including natural products, in a short period of time by HTS attracted attention of many workers. Various detection techniques like fluorescence resonance energy transfer (FRET), Homogeneous time resolved fluorescence (HTRF), etc are available, and the screening of more than 100,000 samples per day is possible. With the introduction of robotics, automation and miniaturization techniques, it became feasible to screen 50,000 compounds a day with complex work-stations. High-throughput screening methods are also used to characterize metabolic and pharmacokinetic data about new drugs. With the use of Cassette dosing techniques even the pharmacokinetic data can be assessed for large number of drug candidates, though not free of drawbacks, yet an effective technique to further increase the drug discovery and development rate. The objective of this article is to give an overview to the High-Throughput screening methodologies used in industries as well as in academic research programmes.