In this issue, we will be discussing aspects how the drug discovery field developed from a “black box” approach to the reductionist approach of the one target-one drug approach that became the dominant driving force of drug discovery in the late 20^th and early 21^st century. The reductionist approach proved very successful, yet did not suit every therapeutic area and more recently there has been a significant interest in adopting more holistic approaches. Advances in technology and biology has finally turned full circle as whole animal models have been reestablished in the drug discovery project map.  They now form a useful adjunct to the standard repertoire of approaches for hit identification.

The free downloads available in this newsletter highlight some of the most recent developments in phenotypic screening. I will elaborate on them below.

The first article, by Wei Zheng, Natasha Thorne and John C. McKew of the National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, USA, entitled “Phenotypic screens as a renewed approach for drug discovery” describes how high throughput methods can be applied to industrialize the process of cancer drug discovery using IHC. The article indicates that the number of approved drugs discovered using such screens has recently exceeded those coming from the reductionist, molecular targeted approach. They suggest that phenotypic screens may improve drug approval rates in the future.

The second article, by Murielle Mimeault and Surinder K. Batra of the Department of Biochemistry and Molecular Biology, College of Medicine, Eppley Cancer Institute, University of Nebraska Medical Center, Omaha, USA entitled: “Emergence of zebrafish models in oncology for validating novel anticancer drug targets and nanomaterials” , extends and expands some of the themes outlined in the first paper and describes the particular value of the approach in testing novel anticancer agents.

Finally, is the review from José  L. Medina-Franco, Marc A. Giulianotti, Gregory S. Welmaker and Richard A. Houghten of the Torrey Pines Institute for Molecular Studies, Florida, USA, entitled: “Shifting from the single to the multitarget paradigm in drug discovery”.  They discuss drug repurposing, polypharmacology and genomics with respect to phenotypic screening and how testing mixture-based libraries is shifting the current paradigm of drug discovery.  Drug repurposing, polypharmacology, chemogenomics, phenotypic screening and high-throughput in vivo testing of mixture-based libraries are shifting today’s current paradigm of drug discovery. Furthermore, the goals of lead identification are being expanded accordingly to identify not only ‘key’ compounds that fit with a single-target ‘lock’, but also ‘master key’ compounds that favorably interact with multiple targets (i.e. operate a set of desired locks to gain access to the expected clinical effects).

Steve Carney was born in Liverpool, England and studied Biochemistry at Liverpool University, obtaining a BSc.(Hons) and then read for a PhD on the Biochemistry and Pathology of Connective Tissue Diseases in Manchester University, in the Departments of Medical Biochemistry and Histopathology. On completion of his PhD he moved to the Kennedy Institute of Rheumatology, London, where he worked with Professor Helen Muir FRS and Professor Tim Hardingham, on the biochemistry of experimental Osteoarthritis. He joined Eli Lilly and Co. and held a number of positions in Biology R&D, initially in the Connective Tissue Department, but latterly in the Neuroscience Department. He left Lilly to take up his present position as Managing Editor, Drug Discovery Today, at Elsevier. He has authored over 40 peer-reviewed articles, written several book chapters and has held a number of patents.