Next Generation Phenotypic Screening: Part of a balanced strategy for accelerating drug discovery
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چکیده
Historically, drug discovery has employed mainly “phenotypic” approaches—often characterized by physiological observations on whole animals or organ models (Kotz 2012). Most of the first-in-class medicines, those that use a unique mechanism of action to treat a medical condition, developed before the 1980s were discovered by phenotypic Executive Summary With the advent of increasingly high throughput biochemistry and molecular biology based assays in the context of the genomics era, the predominant drug discovery strategy in the pharmaceuticals industry has evolved from an empirical or phenotypic approach, to molecular or target-based discovery. Surprisingly, this shift not only failed to accelerate discovery of new first-in-class medicines, it has led to overall higher attrition rates for new compounds and biologics than before the shift. With this realization, the industry is now evaluating how to implement a more holistic approach that incorporates both discovery modes, depending on the available mechanistic information and experimental models. Technology innovations were crucial to the shift from phenotypic to target-based discovery and will again be important in enabling this newly emerging balanced strategy. We will briefly review major pharmaceutical companies that have expanded the use of phenotypic drug discovery and examine the challenges of phenotypic screening, including the remaining technology gaps and underserved model systems.
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تاریخ انتشار 2014