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The Current issue of “The view from here” is concerned with Therapeutics

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The advantage of choosing a topic like therapeutics for a monthly newsletter is multifold. First, it gives me a lot of scope to pick excellent articles as, I suppose, “therapeutics” is the bread and butter of the journal. It does, however, have one more great advantage over other topics that are featured in the journal. That advantage is the ability to select important, but niche pieces of science that perhaps we don’t have the opportunity to highlight as a particular theme. Often these important articles may later prove to be widely important and impact on various aspects of drug discovery. I guess that it is the case of mighty oaks from acorns grow. So in this newsletter, I’ve selected under the broad umbrella of “therapeutics” three top class articles which I suspect would have been difficult to place into specific categories. I think they are very interesting and thought-provoking and I hope that you enjoy them. 

The first article in this month’s offering is entitled: “Interfering peptides targeting protein–protein interactions: the next generation of drugs?”, by Heriberto Bruzzoni-Giovanelli, Valerie Alezra, Nicolas Wolff, Chang-Zhi Dong, Pierre Tuffery and Angelita Rebollo of various institutions from Paris, France. In this article, the authors point out that molecules capable of disrupting protein-protein interactions have the potential to interfere with pathways that perhaps would be difficult to drug using traditional low molecular weight organic molecules. They introduce the concept of interfering peptides and how, due to their chemical and physicochemical nature, such molecules can better disrupt protein-protein surface interactions. They highlight some proof-of-concept examples of the approach, but perhaps the real thrust and importance of the article relates to various strategies to identify potential interfering peptides by in silico, physicochemical and biological efforts. The authors go on to discuss this approach as a potential approach for novel drug design and highlight the benefits and limitations of the technology.

The second article in the series deals with a more specific target than our first. It is by Tim Koopmans and Reinoud Gosens of the University of Groningen, The Netherlands and is entitled: “Revisiting asthma therapeutics: focus on WNT signal transduction”. They give an overview of asthma as a disease that develops due to a combination of allergy and environment. Research has highlighted a number of potential candidate genes for therapeutic intervention, but one of the more interesting potential targets is that involved in lung development via the Wingless/Integrase-1 (WNT) signalling pathway. This pathway has attracted significant attention in other diseases, but not to any great extent in asthma until relatively lately. The review looks back on asthma drugs and debates whether the WNT signaling pathway is of value in the development of novel asthma therapeutics.

And finally, we return to a specific therapeutic target and a very familiar group of diseases. The article deals with the protein kinase, haspin and the development of specific, selective inhibitors against it. Haspin, a serine/threonine kinase that phosphorylates threonine 3 of histone 3 has been implicated in the maintenance of normal mitosis. It has been postulated that selective inhibition of the enzyme will have significant anti-tumoral effects with a reduction in off target side effects since the enzyme only phosphorylates a single threonine very near the protein terminus. The authors review the properties of currently known haspin inhibitors 

 

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.

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