With the PD2 initiative – or Phenotypic Drug Discovery – Lilly opened access for the first time to its internal panel of disease-relevant phenotypic modules, which query complex cellular systems instead of specific targets. The possible advantage resides in the fact that a relevant biological context is interrogated without predisposed bias toward mechanism(s). Thus an opportunity is created to identify compounds that may interact with one or more targets or pathways not anticipated by a single mechanism-driven hypothesis. In essence, phenotypic approaches screen multiple mechanisms and targets simultaneously. Furthermore, since the initial readouts from cellular assays are more information-rich, the connection of compound action to disease-relevant phenotypes is established earlier in the drug discovery process. The challenge with phenotypic drug discovery ultimately lies in the complexity of fully understanding and assessing compound differentiation and elucidating with greater resolution the possible mechanisms of action. Fortunately, this complexity has been substantially reduced with the development of advanced assay technologies and informatics tools that make these challenges tractable for drug discovery. The PD2 initiative relies heavily on these types of tools and makes sophisticated, disease-relevant assays available to participants that would otherwise lack access to well validated means of evaluating their compounds.
With the implementation of the TargetD2 initiative, Lilly expands access to a panel of well-validated target-based assays plus relevant computational methods that will allow participants to engage in meaningful structure design cycles. The TargetD2 initiative – or Target Drug Discovery - focuses on evaluating a disease hypothesis through the process of discovery and clinical testing of a molecule designed to interact with a specific genomic target believed to be involved in the disease pathogenesis. With the sequencing of the human genome and the development of many high throughput and complimentary drug discovery technologies, target-based drug discovery has been the primary strategy of many pharmaceutical companies during the past 20 years. This approach has been advanced by the development of computational and informatics tools that aid scientists in the design, selection and optimization of molecules for specific enzymes, receptors and other bioactive proteins.