I hope that you all had a very pleasant holiday and have returned to work refreshed. I would guess, from the volume of submissions to the Drug Discovery Today EVISE site, there was a lot of desk clearing at the end of the year and a similar amount of New Year’s resolutions early in this year, judging by the volume of activity. If you fall into either category, I apologise for any delay you may have encountered and I guarantee that (in the words of the BBC) “normal service will be resumed as soon as possible”. I thought I’d start 2019 with a topic that I suspect, either directly or indirectly, affects pretty much everyone in the Pharmaceutical industry.  That topic, perhaps unsurprisingly in view of the header of this message is “Targets”. This is fundamentally underpins all pharmaceutically, since if you have not selected and validated your target appropriately, even the most selective, potent and side effect-free compound may well prove to be the cure for no-known disease. This month’s offering has three articles that differ widely with respect to content, one being a general overview of targets and target selection, with the others covering specific targets and the path towards development of drugs against very significant diseases.

The first free download from this newsletter specifically covers the field of safety assessments related to targets. In: “Understanding drug targets: no such thing as bad news”, the author, Ruth Roberts of ApconiX, Alderley Edge, UK discusses how understanding of potential safety risks associated with a target can help to obviate future failure of projects as a result of insufficient therapeutic window and risk/benefit ratio. Although to many of you this might sound like a truism and somewhat obvious, insufficient data related to target safety still dogs the industry and represents a major obstacle to advancing chemical compounds. The author proposes that conducting appropriate target-safety reviews early in a project is essential in reducing project risk and allows better selection of higher-quality targets.

The second article returns to a (perhaps) more familiar style of review, covering the benefit of influencing particular cell types rather than specific receptors or proteins as a more holistic approach to the development of treatments against disease. The article: “Retinal pigment epithelial cells as a therapeutic tool and target against retinopathies” from Barbara Pavan and Alessandro Dalpiaz of University of Ferrara, Ferrara, Italy discusses how the retinal pigment epithelium is a monolayer, largely responsible for providing photoreceptor function, while acting as the main player of the blood/retinal barrier. As such, the epithelium is a major influencer of photoreceptor homeostasis, and drug delivery. Degeneration of this structure has a profound effect on the renewal of photoreceptors and retinal neurons, which, taken as a whole, can seriously compromise vision and result in blindness. The authors indicate possible tools to engineer this cell type in order to reestablish the epithelium, and more naturally reactivate its barrier function and ability to continue to provide retinal cell precursors.

Finally, we cover a much more orthodox “target”-type article. Entitled “Drug targeting of one or more aminoacyl-tRNA synthetase in the malaria parasite Plasmodium falciparum” by Yogavel Manickam, Rini Chaturvedi, Palak Babbar, Nipun Malhotra, Vitul Jain and Amit Sharma of theInternational Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi 110067, India and The Nuffield Department of Medicine, University of Oxford, UK. Covers an approach to dealing with malaria, which, even today represents a major public health issue, especially in the developing world. As drug resistance to standard antimalarial drugs increases in prevalence, even to the mainstay of one of the drugs, artemisinin, which has been in no small part responsible for the recently-observed reduction in incidence, the need for alternative drug approaches to treatment is becoming ever more important and necessary. The authors outline a structural-biology-based approach to targeting parasitic aminoacyl-tRNA synthetases to achieve novel approaches to therapy. They propose this as a platform for sustained, significant developments in the fight against malaria.

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. On the media front, Dr. Carney has been busy on some hush-hush projects that will be reported on later in the year.