Target assessment for antiparasitic drug discovery

Abstract

Drug discovery is a high-risk, expensive and lengthy process taking at least 12 years and costing upwards of US$500 million per drug to reach the clinic. For neglected diseases, the drug discovery process is driven by medical need and guided by pre-defined target product profiles. Assessment and prioritisation of the most promising targets for entry into screening programmes is crucial for maximising the chances of success. Here, we describe criteria used in our drug discovery unit for target assessment and introduce the 'traffic-light' system as a prioritisation and management tool. We hope this brief review will stimulate basic scientists to acquire additional information necessary for drug discovery.

Figure 1. ‘Good‘ and ’bad‘ pockets for binding of drug-like molecules

(a) An example of a poorly druggable protein (Hepatitis C serine protease) with a shallow featureless active site (PBD code 2A4R) [57]. (b) An example of a highly druggable active site (spleen tyrosine kinase) with a deep pocket allowing an inhibitor (Gleevec) to be significantly buried (PBD code 1XBB) [58]