The Current issue of “The view from here” presents Phenotypic Screening

The topic of this month’s newsletter from Drug Discovery Today is “Phenotypic screening”.

What goes around comes around. What seems like not so long ago, although it is well over 30 years, I remember the days of screening compounds in rats, in a model called rat adjuvant arthritis. At the time, it was the best we had and commercial pressures to deliver were not nearly so acute as they are today. Times changed and soon such a time-consuming, low-throughput system for testing compounds was not practical for the pharmaceutical industry. The industry became so much more “mechanistically” driven and this allowed the high throughput screening (HTS) of many millions of compounds. Sheer nirvana. Or was it? It became ever clearer that although HTS provided the means to screen more compounds than you could ever have imagined, the trend moved towards more thoughtful library design and the screening of cassettes of compounds that made more biological or chemical “sense”. Although still the mainstay of many drug discovery programmes, many drug discovery professionals were interested in the more intricate chemical interplay of biological systems, rather than just the interaction of a compound with a particular target protein. Advances in biology and robotics, however, allowed technologies to be developed that were capable of providing a more holistic estimation of a compound’s effect in a more physiological system. Not exactly a rat. But a more relevant physiological system perhaps. In any case, we have published some excellent reviews on and around the subject in the last few months in Drug Discovery Today and I wanted to highlight them to you.

The first article, by Markus Schirle and Jeremy L. Jenkins   of Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA  is  entitled: “Identifying compound efficacy targets in phenotypic drug discovery” and they outline Available approaches to target deconvolution and how they can be grouped based on underlying principles and should be used in combination to exploit their complementarity in efforts toward understanding compound mechanism of action.

The second article, from Andrea L. Gonzalez-Munoz, Ralph R. Minter and Steven J. Rust of the Department of Antibody Discovery and Protein Engineering, MedImmune, Milstein Building, Granta Park, Cambridge CB21 6GH, UK entitled: “Phenotypic screening: the future of antibody discovery” describes how  drug screening based on phenotype, rather than target, is currently an undervalued approach for antibody discovery. In this review, they find significant opportunities in accessing novel target space through phenotypic antibody discovery.

Finally, is the article from Wei Zheng, Natasha Thorne and John C. McKew, of National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Bethesda, MD 20892-3370, USA, entitled: “Phenotypic screens as a renewed approach for drug discovery“ The article discusses how, phenotypic screening is gaining new momentum in drug discovery with the hope that this approach may revitalize drug discovery and improve the success rate of drug approval through the discovery of viable lead compounds and identification of novel drug targets.

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. Currently, he also holds an honorary lectureship in Drug Discovery at the University of Surrey, UK. He has authored over 50 articles in peer-reviewed journals, written several book chapters and has held a number of patents. Currently no news on the tenor horn front.

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