I guess it is too late to wish all of our readers a happy new year, but better late than never, so I hope that you all had a very happy new year. Anyway, now it is time to get back to the business of drug discovery and what better place to start than medicinal chemistry? Medicinal Chemistry has been the mainstay of the industry since its earliest incarnations. Despite the impact of biological therapies for disease, medicinal chemistry has continued to have a key role in the industry, albeit in a modified way. The articles in this newsletter reflect some of the changes in the day-to-day life of a jobbing chemist. We examine the insights of a major medicinal chemistry group in their search for hits in the neuroscience arena. Following that, is a more theoretical and predictive approach to the hunt for active compounds and finally how a well-established technique is now used to explore various aspects of drug discovery and development. I hope that you enjoy them. 

The first article in this month’s offering is entitled: “Industrial medicinal chemistry insights: neuroscience hit generation at Janssen”, by Gary Tresadern, Frederik J.R. Rombouts, Daniel Oehlrich, Gregor Macdonald and Andres A. Trabanco of Janssen Belgium and Spain. In this article, the authors explain how modern medicinal chemistry impacts drug discovery in many ways beyond just optimization of clinical candidates. They describe the formation and work of a small team dedicated to hit and lead generation with novel methods inside Janssen. 

The second featured article is by Glyn Williams, György G. Ferenczy, Johan Ulander and György M. Keseru of Astex, AstraZeneca and The Hungarian Academy of Science. It is entitled: “Binding thermodynamics discriminates fragments from druglike compounds: a thermodynamic description of fragment-based drug discovery”. The article discusses the topic of fragment-based drug discovery, they look at a large library of fragment molecules and examine the relationship between binding thermodynamics to protein targets. They propose that such information on binding thermodynamics may provide an insight into the relationships of particular fragments to overall protein-ligand interactions and, hence, to prioritise particular fragments in compound design. 

Finally, we come to the article “Mechanistic applications of click chemistry for pharmaceutical drug discovery and drug delivery”  From Nilesh M. Meghani, Hardik H. Amin and Beom-Jin Lee from the Ajou University, Korea. This paper discusses the mechanistic applications of the established technique of Click Chemistry to the discovery and development of novel pharmaceutical agents. The article further discusses the use of the technology in drug delivery and diagnostics. An earlier review by Sharpless and Kolb on click chemistry has been the highest ever cited article in Drug Discovery Today, with currently 2109 citations and continues to be one of our most cited and downloaded articles, having first been published in 2003.

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.