Sandra Fox

High-throughput screening: update on practices and success.

High-throughput screening (HTS) has become an important part of drug discovery at most pharmaceutical and many biotechnology companies worldwide, and use of HTS technologies is expanding into new areas. Target validation, assay development, secondary screening, ADME/Tox, and lead optimization are among the areas in which there is an increasing use of HTS technologies. It is becoming fully integrated within drug discovery, both upstream and downstream, which includes increasing use of cell-based assays and high-content screening (HCS) technologies to achieve more physiologically relevant results and to find higher quality leads. In addition, HTS laboratories are continually evaluating new technologies as they struggle to increase their success rate for finding drug candidates. The material in this article is based on a 900-page HTS industry report involving 54 HTS directors representing 58 HTS laboratories and 34 suppliers.

High Throughput Screening for Drug Discovery: Continually Transitioning into New Technology

Those working in HTS laboratories, pressured to find increasing numbers of drug leads while containing costs, are seeking larger compound sets, more automated systems to screen them faster, and an integrated set of equipment and consumables. Enabling technologies are continually being developed and suppliers are teaming up to supply integrated equipment and consumable sets. Miniaturization, microfluidic chips, subnanoliter dispensing, fluorescence, homogeneous assays for HTS, and virtual screening are just some of the evolving tools that HTS experts are continually evaluating and incorporating into drug discovery operations.

High-throughput screening: searching for higher productivity.

HOW DRUG DISCOVERY EFFORTS are managed within highthroughput screening (HTS) laboratories worldwide varies, with different approaches, tools, and strategies being applied. Because a significant number of HTS laboratories have been in existence for 8 to 10 years, many in the industry are disappointed that few drug candidates, originally screened in HTS, have made it to the market. However, it has been a steep learning curve. Only in the past few years have HTS scientists been able to bring together sophisticated automated equipment, robust assays, validated targets, high-quality compound libraries, useful data analysis tools, and a better understanding of how to use HTS within the whole of drug discovery. HTS is beginning to show its strength. A recent worldwide study involving 51 HTS directors reporting for 53 laboratories and 39 suppliers, High Throughput Screening: Improving Strategies, Technologies, and Productivity, documents current HTS successes. Altogether, 74 clinical candidates, leads originally found in HTS laboratories, were reported by the HTS directors participating in the study. Two of these products are on the market. The material in this article is based on this 850-page industry report published in December 2003.