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Pharma Tech Outlook | Wednesday, November 24, 2021
FREMONT, CA: While the process of drug discovery is rewarding, it is a complicated journey fraught with uncertainty. The process begins with the understanding of an unmet need in a disease or therapeutic area. Once a "druggable" target is identified, the drug screening process begins. Drug screening aims to identify molecules that can interact with the target or facilitate the desired phenotypic response.
Combinatorial chemistry and molecular biology advancements have facilitated the identification of many molecular targets, necessitating the development of novel screening approaches.
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This article discusses several of the various screening strategies used during the drug discovery process. Additionally, significant advancements and challenges associated with the techniques are discussed.
High-throughput screening in the discovery of new drugs: High-throughput screening (HTS) is a technique that is frequently used in the early stages of drug discovery. HTS is used to identify "hit" molecules that exhibit activity against a target of interest in large compound libraries containing thousands of molecules. Once found, these hit molecules are confirmed and modified to generate lead compounds with increased selectivity and potency. These lead compounds can then be investigated further to identify a possible therapeutic candidate for preclinical testing. HTS entails detecting, tracking, and quantifying events through robotics, liquid/microplate handling systems, and microplate readers. Additionally, it necessitates the use of specialized software for instrument control and data processing.
While HTS is a crucial technique, it can be tough to determine pharmacological attributes such as toxicity and bioavailability. HTS is generally used to aid in lead optimization—think of it as a rapid scan of biological entities in which candidates with little or no effect can be quickly filtered out.
High-content screening—Advancing high-throughput screening: High-content screening (HCS), a technique initially developed to supplement HTS, has exploded in popularity in recent years. HCS combines the scalability of high-throughput techniques with the sensitivity of cellular imaging to acquire quantitative data from complex biological systems.
HCS enables simultaneous examination of multiple properties of individual cells or organisms. To extract data from cell populations, automated microscopy, image processing, and visualization tools are combined. HCS is typically based on high-throughput fluorescence imaging of samples and generates quantitative reports on various specifics such as the spatial distribution of targets and the morphology of individual cells and organelles.
Currently, the majority of HCS is performed using conventional or two-dimensional (2D) tissue culture. However, 3D cell culture models are being investigated as well. By enhancing physiological relevance, 3D models have the potential to reshape the HCS landscape.
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