ABSTRACT
There are three basic components necessary for drug discovery and lead identification: (1) targets, (2) screens and (3) compounds. Each of these plays a pivotal role in the drug discovery process and ultimately the success of clinical trials. During the past 50 years there has been a paradigm shift in drug discovery (Fig. 1), closely bound to the development of technology [1]. Initially, companies focused on the effects of putative therapeutics on whole-animal models to study pharmacology and efficacy. Later, tissue and cell cultures led to a refinement in pharmacological studies and in the number of screenings performed. More recent progress has involved advanced purification and molecular biology technologies, which in the past 10 years has lead to a wholesale move toward selecting molecular targets to screen. Most recent, there has been an explosion of genomics, proteomics, bioinformatics, and information technologies, which will significantly increase the potential to identify and validate novel disease genes and their corresponding pathways, representing enormous value to the pharmaceutical industry. Of the approximately 80,000-150,000 human genes, there may be as many as 10,000 potential “drugable” targets, i.e., amenable to low molecular weight molecules (e.g., enzymes, receptors, ion channels, hormone receptors, etc.) for treatment of the most common multifactorial diseases [2].
