Phenotypic screening techniques for drug discovery.

: Two landmark epidemiological studies identified spp. as a significant cause of diarrheal disease in pediatric populations in resource-limited countries. Notably, nitazoxanide is the only approved drug for treatment of cryptosporidiosis but shows limited efficacy. As a result, many drug discovery efforts have commenced to find improved treatments. The unique biology of presents challenges for traditional drug discovery methods, which has inspired new assay platforms to study parasite biology and drug screening. : The authors review historical advancements in phenotypic-based assays and techniques for drug discovery, as well as recent advances that will define future drug discovery. The reliance on phenotypic-based screens and repositioning of phenotypic hits from other pathogens has quickly created a robust pipeline of potential cryptosporidiosis therapeutics. The latest advances involve new culture methods for oocyst generation, continuous culturing capabilities, and more physiologically relevant assays for testing compounds. : Previous phenotypic screening techniques have laid the groundwork for recent cryptosporidiosis drug discovery efforts. The resulting improved methodologies characterize compound activity, identify, and validate drug targets, and prioritize new compounds for drug development. The most recent improvements in phenotypic assays are poised to help advance compounds into clinical development.