Target Validation: Linking Target and Chemical Properties to Desired Product Profile

Paul      G. Wyatt; Ian      H. Gilbert; Kevin      D. Read; Alan      H. Fairlamb

Abstract

The discovery of drugs is a lengthy, high-risk and expensive business taking at least 12 years and is estimated to cost upwards of US$800 million for each drug to be successfully approved for clinical use. Much of this cost is driven by the late phase clinical trials and therefore the ability to terminate early those projects destined to fail is paramount to prevent unwanted costs and wasted effort. Although neglected diseases drug discovery is driven more by unmet medical need rather than financial considerations, the need to minimise wasted money and resources is even more vital in this under- funded area. To ensure any drug discovery project is addressing the requirements of the patients and health care providers and delivering a benefit over existing therapies, the ideal attributes of a novel drug needs to be pre-defined by a set of criteria called a target product profile. Using a target product profile the drug discovery process, clinical study design, and compound characteristics can be defined all the way back through to the suitability or druggability of the intended biochemical target. Assessment and prioritisation of the most promising targets for entry into screening programmes is crucial for maximising chances of success.

Keywords: Chemical validation, druggability, drug resistance, genetic validation, neglected diseases, molecular targets, target assessment, target product profile, discovery of drugs, paramount, vital, biochemical target, vector-borne parasitic diseases, African sleeping sickness, molecular target approach