Use of cell culture in drug discovery

Author: 
Nisaath Begum, Sujith, S., Devu B Nair and Nisha, A.R.

The first step in drug discovery is, in many cases is to test compounds in cell culture to find out the activity in terms of pharmacological actions. In vitro cell culturebasedstudies in the non-clinical laboratory serve various functions along the path from the discovery of new molecular entities to approval and marketing of a therapeutic. Various techniques have been developed to study many aspects of drug disposition including absorption, metabolic stability, elucidation of elimination pathways, potential for inhibition and induction of CYP450 enzymes, metabolite profiling in various model species and humans. Typically, this means that the drug product must undergo a series of robust tests and experiments using in vitro, in vivo, ex vivo, and in silico models as per the needs of the focused indication and regulatory guidelines. A thorough understanding of the metabolic profile in various species and man is crucial in successful evaluation of potential of new therapeutics. This is also particularly important as it will assist in minimizing dosing levels in toxicology studies which are chosen on the basis multiples of the pharmacologically effective doses. For pharmacokinetic in vitro absorption, distribution, metabolism and excretion (ADME) studies, various models of cell lines grown in 2D are generally used. Human colon carcinoma cells (Caco-2) are used for absorption analyses, and canine kidney cells (MDCKII-MDR1) are generally employed in distribution studies, while hepatocytes are utilized in metabolism and excretion investigation. The pharmaceutical industry presently relies on several widely used in vitro models, including two-dimensional and three-dimensional cell culture models.

Paper No: 
4660