The Effect of Cell-based Assay on Drug Discovery Research

Posted by beauty33 on December 15th, 2021

Cell-based assays (CBA) can be used to measure the response of cells to drug compounds or external stimuli to overall cell function. The effect of the drug depends on the concentration, the binding site and the mechanism of action within the perturbation of various organelles. In addition, various chemical, biological and environmental factors can regulate biological processes and cell functions, such as the production of reactive oxygen species in mitochondria and redistribution of phospholipids into the plasma membrane of daughter cells during proliferation. Therefore, cell-based testing is often used in cytotoxicity testing to determine the mechanism of action (MOA), early evidence of drug screening, and to determine its biological relevance and physiological importance.

For decades, cell-based drug screening analysis has been widely used in drug discovery research to select promising lead compound candidates from hundreds of thousands of compound libraries. Combining advanced microscopes with CBA, high-content screening (HCS) can be used to measure many characteristics of a single cell at the same time. Broadly speaking, HCS refers to any CBA that measures report signals, morphological analysis, and phenotypic analysis, all of which are used to measure the response of cells to controlled stimuli. High content screening (HCS), also known as high content analysis or (HCA), is a cell biology method that combines automated imaging and quantitative data analysis in a high-throughput format, suitable for large-scale applications such as drug discovery research. High content Screening is a high-throughput screening (HTS) in which various phenotypic indicators are quantified.

Compared with in vitro biochemical analysis, cell-based analysis provides valuable information in biological and physiological environments. There are many different types of cell-based tests, some of which include second messenger tests, reporter gene tests, and cell proliferation tests. These tests are commonly used in compound screening projects in early drug discovery studies. Cell-based testing can distinguish between agonists and antagonists, identify modulators, and provide direct information about the compound. This information relates to cell permeability, intracellular stability, and compound-related acute cytotoxicity.

Creative Bioarray has developed a wide range of detection methods to evaluate the effects of xenobiotics on various cell perturbations, with special emphasis on plasma membrane, lysosome, mitochondria and nuclear compartments, and receptor-triggered endoplasmic reticulum calcium mobilization. Fluorescence methods have higher sensitivity and are easier to miniaturize, and are used for large-scale or high-throughput measurement of cell viability, pathway activation, toxicity, and phenotypic cell responses to exogenous stimuli. The fluorescence method of CBA was originally developed using small, highly fluorescent organic molecules to monitor ion concentration and membrane potential.

Cell-based assays using primary cells or immortalized cancer cell lines is not sufficient to develop effective cancer treatments. The latest advances in stem cell research have revolutionized the drug discovery process. Cancer stem cells are produced by oncogenic transformation of stem cells or progenitor cells, and can be isolated from tumors and used as an effective platform for cancer drug screening. Embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC) can provide an unlimited source of normal human cells, which can be used for drug screening and toxicology research. The latest development of iPSC has completely changed the field of stem cells. iPSCs are pluripotent cells that are artificially derived from somatic cells (for example, fibroblasts and other adult cell types) by inducing a small set of powerful pluripotency genes.

Creative Bioarray has used molecular biology tools to develop a variety of cell models related to advanced diseases. Advances in microtechnology have led to the development of new cell-based disease models, micro-printed tumor spheres, tissue on a chip, and multicellular organoids. All these innovations bring great hope for the discovery of a new generation of therapies.