Happy Christmas to all of our readers from everyone at Drug Discovery Today. In this issue of Editor’s Choice, I will be featuring the most downloaded articles published in Drug Discovery Today in 2013.
In the first Quarter of the year, the most downloaded article was: “Shifting from the single to the
multitarget paradigm in drug discovery” by José L. Medina-Franco,Marc A. Giulianotti, Gregory S. Welmakerand Richard A. Houghten. This article challenges the long-held data reductionist approach and instead discusses the concepts of drug repurposing, polypharmacology, chemogenomics, phenotypic screening and high-throughput in vivo testing of mixture-based libraries in an integrated manner. These research fields offer alternatives to the current paradigm of drug discovery, from a one target–one drug model to a multiple-target approach.
The paper: “Three-dimensional cell culture: the missing link in drug discovery”, by Susan Breslin and Lorraine O’Driscoll, deals with the very important topic of cell behaviour in 2D and 3D gels and discusses the pros and cons of both systems with particular respect to screening anti-cancer agents.
In the final article, the most downloaded of the 3rd Quarter of 2013, Albert C. Pan, David W. Borhani, Ron O. Dror and David E. Shaw discuss the pharmacologically-significant topic of Molecular determinants of drug–receptor binding kinetics. It is obvious, although often ignored, that molecules will (generally) only exert their desired pharmacological effect when bound to their target. Until relatively recently, however, it was not possible to directly determine the amount of ligand bound to target at tissue equilibrium. The article discusses the molecular determinants of drug-receptor binding kinetics, which are relatively unknown compared with the molecular determinants of drug-receptor affinity.
In common with other years, these articles share a theme in that they are all involved with fundamental issues of drug design: a movement away from a reductionist approach in selecting compounds for the treatment of diseases; enhancing the validity and predictive value of in vitro cellular assays and novel approaches related to the improvement of drug molecules through enhanced design.
We hope that we can continue to publish review material from established and up-and-coming researchers that will challenge the way that you currently perform drug discovery. It is only from challenging the norm that true advances will be established.
I hope that you and your families have a wonderful Christmas break and that you come back to work refreshed and invigorated to develop the groundbreaking drugs of the future.
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.