The development of high-content screening (HCS) technology and its importance to drug discovery

ABSTRACT

Introduction: High-content screening (HCS) was introduced about twenty years ago as a promising analytical approach to facilitate some critical aspects of drug discovery. Its application has spread progressively within the pharmaceutical industry and academia to the point that it today represents a fundamental tool in supporting drug discovery and development.

Areas covered: Here, the authors review some of significant progress in the HCS field in terms of biological models and assay readouts. They highlight the importance of high-content screening in drug discovery, as testified by its numerous applications in a variety of therapeutic areas: oncology, infective diseases, cardiovascular and neurodegenerative diseases. They also dissect the role of HCS technology in different phases of the drug discovery pipeline: target identification, primary compound screening, secondary assays, mechanism of action studies and in vitro toxicology.

Expert opinion: Recent advances in cellular assay technologies, such as the introduction of three-dimensional (3D) cultures, induced pluripotent stem cells (iPSCs) and genome editing technologies (e.g., CRISPR/Cas9), have tremendously expanded the potential of high-content assays to contribute to the drug discovery process. Increasingly predictive cellular models and readouts, together with the development of more sophisticated and affordable HCS readers, will further consolidate the role of HCS technology in drug discovery.

KEYWORDS:

• Cell-based assays
• high-content screening
• phenotypic drug discovery
• target identification

Article highlights

• The development of high-content screening (HCS) field relies on technical advances in instruments and biological models.

• Recently, more and more physiologically relevant models have been introduced in HCS assays including primary cells, engineered cell lines, 3D-cell cultures and whole organisms.

• In recent years, a number of molecular tools and novel analytical methods are being developed to exploit the multiparametric nature of HCS technology.

• HCS technology is now a fundamental tool both in phenotypic drug discovery and in target-based drug discovery.

• Applications of HCS can be found in many therapeutic areas and across the whole preclinical development process.

This box summarizes key points contained in the article.

Acknowledgements

The authors thank Arturo Galvani for critical reading of the manuscript.

Declaration of interest

The authors are employees of Nerviano Medical Sciences Srl. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.