Drug Repositioning: Principles, Resources, and Application of Structure-Based Virtual Screening for the Identification of Anticancer Agents

Abstract The process of drug development is a complex and expensive process; spanning over several years of painstaking research and involving millions of dollars, a candidate ligand goes through rigorous clinical trials before it can finally hit the market. Although all novel drugs undergo this harsh yet reliable regime of drug discovery, the hour calls for a quick and less expensive way to identify drugs that could be used for the treatment of cancer, one of the most ruthless diseases with an astonishingly low survival rate. One way to get around the problem associated with time is through the application of high-throughput screening, more precisely computer-aided virtual screening with molecular docking. This method involves scanning and testing of large compound libraries to check and see if they perform the desired function after binding to a target protein. This method of drug discovery gained notoriety and has been used ever since as it reduces the search time for new compounds drastically when compared to the traditional method of identifying active compounds experimentally. However, the ligands identified through virtual screening still have to undergo the process of optimization and the test for potential toxic effects. An efficient method for tackling this problem lies in the concept of drug repositioning, better known as drug repurposing, which involves discovering new indications for existing drugs, and is a growing field in bioinformatics as it is used to identify indications for existing drugs. By repositioning of drugs, the cost associated with early stages can be reduced, while keeping the drugs safe for human trials. This technique of drug repurposing has been a success in both academia and pharmaceutical companies, which will be discussed in this chapter.