1.5.1 The Drug Discovery Process

Drug discovery — the earlier and scientifically more exploratory portion of the overall pipeline — refers to the process by which a novel therapeutic...

Drug discovery — the earlier and scientifically more exploratory portion of the overall pipeline — refers to the process by which a novel therapeutic concept is converted into a chemically defined lead compound. It typically begins with disease understanding: characterising the pathophysiology of a disease sufficiently to identify a plausible molecular point of intervention. This is followed by target selection and validation, the subject of Phase 2, and by hit generation, in which large compound libraries, natural product extracts, or rationally designed molecules are screened for activity against the chosen target. Drug discovery is distinguished from drug development chiefly by its exploratory, iterative character: many targets and many chemical series are pursued in parallel, and the majority are abandoned before a single lead compound is nominated for the more resource-intensive development phase. Historically, drug discovery relied heavily on serendipity and empirical screening of natural products; contemporary discovery increasingly integrates rational, structure-based design, computational modelling, and genomic target validation, considerably improving the efficiency with which viable leads are identified.