ABSTRACT
Historically, the pharmaceutical industry has used two alternative approaches to drug discovery: phenotypic screening and target-based or hypothesis-driven screening. This chapter presents the illustrations of cost-effective, risk-mitigated, drug repositioning by phenotypic screening using MLR-1023 for diabetes and MLR-1019 for PD-LID as examples. The alternative to target-based or hypothesis-driven screening is phenotypic screening, in which a drug candidate is evaluated in a biological system, be it a culture, cell system, isolated organ, whole animal, or human. One potential solution to narrow this gap is to augment target-based screening with phenotypic screening. Even in a therapeutic area such as CNS disease, where animal models are somewhat limiting as mentioned here, phenotypic screening has been used to identify essentially all of the first-in-class CNS therapeutics and will continue to serve the field in the future. In vivo phenotypic screening provides the most fertile platforms for drug repositioning, including pre- and postmarketing human clinical trials and preclinical experimental animal models of diseases.
