Opportunities and Challenges in Antiparasitic Drug Discovery

Abstract

New impetus has been given to antiparasitic drug discovery by the sequencing of several parasite genomes, and by the establishment of new public–private partnerships (PPPs) whose focus is specifically on tropical diseases. New drugs for parasitic diseases need to meet product profiles that are defined in conjunction with those responsible for control programmes in the affected countries, and reflect what is required for use in resource-poor settings. Compound screening against selected molecular targets is increasingly being used in the search for new chemical leads. The quality of the compound libraries being assessed is a key factor in determining success. The majority of successful drugs have come from either evaluating known classes of active compounds or from discovering new indications for known drugs. This approach continues to be an important part of any discovery programme for antiparasitic drugs. Lead compounds need to be optimized so that they have the characteristics required to meet product profiles. As in most drug discovery projects, this is often the rate-limiting step. Compounds will need to be tested in several animal models with careful consideration given to formulation. The recent entry of a new synthetic peroxide antimalarial into clinical trials illustrates how public funding for a diverse set of early-stage discovery projects led to a set of good lead compounds that were selected for further development by a PPP. Early-stage discovery research needs further strengthening and will require financial support from public sources. Antiparasitic drug discovery and development is not primarily market-driven, and so partners from organizations with differing cultures and underlying objectives need to work together. The role in such partnerships of researchers, public-health officials and industry leaders from disease-endemic countries needs to be increased.