Kinase Targets and Inhibitors in Inflammation, 2007 PDF Download

Author: Khusru Asadullah
Publisher:
ISBN: 9788178952574
Category : Anti-inflammatory agents
Languages : en
Pages : 162

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Book Description
Whereas G protein-coupled and nuclear receptors have been in the focus of the pharmaceutical industry since decades, protein kinases became interesting drug targets more recently. Several protein kinase inhibitors are well established for the treatment of tumors in the meantime, many more are in clinical development. Inside into the biology of protein kinases and progress in technologies to target these molecules, however, fostered the discovery and development of protein kinase inhibitors for the treatment of inflammation, too. They are particular promising since they are key factors in signal transduction with major impact for initiating, propagation and regulation of immunological responses. In addition, they are well drugable by small molecular weight inhibitors, opening the chance to discover oral bioavailable drugs. When considering kinases as targets in inflammation, however, there are several issues too. These are mainly the selectivity of both the target and the inhibitor and the associated side effect profile of corresponding drugs. In contrast to application in oncology where efficacy is more or less the most important criteria, a high safety profile is key for the chronic treatment of usual non-life treating inflammatory and autoimmune diseases. Having said this, however, clearly better drugs with a favorable therapeutic index (effect / side effect ratio) are needed for these indications, too. Thus, to be considered as a really promising drug target the protein kinase of interest should be significantly involved in the inflammatory process - otherwise insufficient efficacy and potency would have to be expected - without being involved in other physiological processes of essential biological importance or a very selective expression pattern. The same is true with the specifity of the inhibitors itself. So a compound hitting just one other kinase a little may not be acceptable, depending on the function of these off target molecule. Consequently, a solid target identification and validation is needed before lead identification and optimization with the goal of achieving high specifity is started. Despite all these challenges major progress has been made and the first promising kinase inhibitors are moving into the clinic for anti-inflammatory therapy. There are many more on the horizon and it s pretty likely that protein kinase inhibitors will enrich the spectrum of therapy for chronic inflammatory and autoimmune diseases. Within this issue an overview is given on recent progress in the field of protein kinase inhibitors for the treatment of inflammation addressing the opportunities and chances on one hand and the issues and hurdles on the other hand. We are very pleased that we were able to convince real experts to contribute to this hot topic issue. Starting with some general points the recent findings are issued and should enabled the reader to keep up with this fast developing field that is of substantial interest for basic and clinical orientated scientists on one hand and academia as well as pharmaceutical industry on the other hand. All chapters in this book have been published before as articles in a hot topic issue of Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Volume 6, Number 1, February 2007 and are reprinted here with permission by Bentham Science Publishers Ltd.