Figure 1.

Target-centric drug discovery and development. The basic target-centric approach involves steps that begin with the investigation of the basic science. Although a holistic approach to the disease has not usually been applied, over the past few years additional information has been gleaned from patient data and network analyses as part of basic scientific information. The next step includes the identification (ID) of a druggable molecular target (i.e., a protein or gene associated with the disease), followed by the validation of this target by showing that modulation of the target has the ability to regulate disease-specific biological processes in in vitro and in vivo disease models. The next step involves the development of an assay measuring target activity, screening of selected libraries, and then the generation of leads from the validated hits. The optimization of leads to increase potency and to build in target specificity follows, and increasingly, the application of early safety and absorption, distribution, metabolism, and excretion testing in vitro. The application of target ID techniques such as chemical proteomics is increasingly being employed to identify additional on-target and off-target interactions. The next step involves preclinical testing with animal models for efficacy, toxicity, and pharmacokinetics. The next step involves phase I to III clinical trials.