Antiparasitics discovery: from genotype to phenotype to compounds

Area of Science:

• Drug Discovery
• Parasitology
• Medicinal Chemistry

Background:

• Antiparasitic drug discovery historically relied on whole-organism screening (phenotypic screening).
• Molecular target-based screening has played a limited role and is often underestimated.
• Few marketed antiparasitic drugs have been discovered solely through molecular target-based approaches.

Purpose of the Study:

• To evaluate the relevance and impact of molecular target-based screening in antiparasitic drug discovery.
• To highlight the successful application of molecular target-based screening in conjunction with phenotypic screening.
• To underscore the value of integrating different screening methodologies for identifying novel antiparasitic agents.

Main Methods:

• Review of historical and current antiparasitic drug discovery strategies.
• Analysis of literature on phenotypic screening versus molecular target-based screening.
• Case studies of successful antiparasitic drugs developed using molecular target-based approaches.

Main Results:

• Phenotypic screening has dominated antiparasitic drug discovery literature.
• Molecular target-based screening has led to the discovery of important antiparasitic drug classes, including isoxazolines, bispyrazoles, depsipeptides, and praziquantel derivatives.
• Successful antiparasitic agents demonstrate the efficacy of the molecular target-based approach when combined with phenotypic screening.

Conclusions:

• Molecular target-based screening is a valuable and effective strategy for antiparasitic drug discovery.
• Integrating molecular target-based screening with phenotypic screening enhances the discovery of novel antiparasitic drugs.
• The perceived lesser relevance of molecular target-based screening is challenged by the success of drugs discovered using this method.