About this Research Topic
In search of more successful approaches, the pharmaceutical industry is moving towards phenotypic screening beyond individual genes/targets. However, this requires rethinking of diseases and drug discovery approaches from a network and system biology perspectives. Since returning to the pre-genomics era of screening drug candidates in laborious animal models is not a feasible solution, the industry needs to evolve a new paradigm of phenotypic drug discovery within the context of systems biology. Such a paradigm must combine physiologically and disease relevant biological substrates with sufficient throughput, operational simplicity and statistical vigor. Biomarker strategies for translational medicine, as well as preclinical safety and selectivity assessments, would also need to be revised to adapt to the target agnostic style.
This focused issue aims to discuss strategies, key concepts and technologies related to systems-based approaches in drug development. Design and implementation of innovative biological assays, featuring multiple target strategies, and rational drug design in the absence of target knowledge during the early drug discovery are illustrated with examples. Specific topics include:
• The need for systems-based approaches in drug development
• Phenotypic screening strategies (cellular, tissue/organ/organism-based phenotypes; parasites, zebrafish model system, iPSC and patient-derived cells; challenges and emerging technologies)
• Compound libraries (natural product inspired compound collections)
• Target deconvolution and identification (RNAi, protein microarrays, chemical genomics, computational methods; challenges and emerging technologies)
• Target agnostic lead discovery and optimization
• Multi-target approaches and decoding the phenotype (understanding biological interactions and multiscale systems modeling)
• Translational aspects
• Early evaluation of selectivity and safety in a target agnostic manner
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