The Current issue of “The view from here” discusses novel therapeutics.

The topic of this month’s newsletter from Drug Discovery Today is novel therapeutics.

The challenge of discovering novel therapeutics is not getting any easier. One might imagine that with advances in technology, would come concomitant reduction in the discovery process. I know that I really don’t need to state that this is far from the truth. For example, the era of antibiotics over the last 70 years or so has brought with it the not inconsiderable problem of antibiotic resistance and the prospect of a future where there is a real possibility of infection becoming the most common cause of death in our society. One cannot overstate the ingenuity of the human race and although infective organisms represent, along with climate change, some of the most challenging problems facing mankind, I have every faith that this will be overcome in the near future. Recent health issues in West Africa highlight how, even now, we are relatively helpless against some of the most primitive residents of this planet. This newsletter highlights some of the efforts directed against microorganisms, cancer and some novel developments in intracellular delivery. A bit of a mixed bag, I would agree, but all highly relevant to the development of drugs against diseases that continue to threaten the human race.

The free downloads available in this newsletter highlight some of the most recent developments in therapeutic development  in drug discovery. I will elaborate on them below.

The first article, by Edwige Picazo and Fabrizio Giordanetto of The Medicinal Chemistry Department, Taros Chemicals, Dortmund, Germany, entitled “Small molecule inhibitors of ebola virus infection” overviews state-of-the-art biological and medicinal chemistry approaches to the discovery of small molecules directed against ebola viral infection.  The article succinctly summarises current lead development, which largely is concentrated on the discovery of viral transcriptional modulators and viral entry and fusion modulators.  The authors describe those approved drugs, those in clinical trials and those in the discovery phases. 

The second article, from Mafalda Rizzuti, Monica Nizzardo, Chiara Zanetta, Agnese Ramirez and Stefania Corti, entitled: “Therapeutic applications of the cell- penetrating HIV-1 Tat peptide” of the Dino Ferrari Centre, Neuroscience Section, University of Milan, Italy, outlines how many promising medicinal chemistry efforts directed against various pathologies, particularly in neurodegenerative disease, is further complicated by tissue and cellular barriers, preventing uptake into the target cell. They describe the conjugation of drug to cell-penetrating peptides, which can deliver their payload to the target cell, even when administered systemically. The authors concentrate upon the biology, classification and mechanisms of internalization of cell-penetrating peptides, in particular the cell-penetrating peptide: HIV-derived Tat peptide, and discuss its efficient but controversial use in basic, preclinical and clinical research from its discovery to the present day.

Finally, is the review from Muhammad Hanif, Maria V. Babak and Christian G. Hartinger  of  The School of Chemical Sciences, University of Auckland, New Zealand, entitled, “Development of anticancer agents: wizardry with osmium”.  The authors discuss how platinates have become the mainstay of many effective cancer therapies. Depending on the choice of ligand system, osmium compounds exhibit diverse modes of action, including redox activation, DNA targeting or inhibition of protein kinases. In this review, they highlight recent advances in the development of osmium anticancer drug candidates and discuss their cellular mechanisms of action.

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 40 peer-reviewed articles, written several book chapters and has held a number of patents. Steve is currently the 197th best second tenor horn player in the world according to 4barsrest (accessed 28th April 2015).

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