Kinase Drug Discovery 鈥?What鈥檚 Next in the Field?

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• 作者：Philip Cohen ; Dario R. Alessi
• 刊名：ACS Chemical Biology
• 出版年：2013
• 出版时间：January 18, 2013
• 年：2013
• 卷：8
• 期：1
• 页码：96-104
• 全文大小：424K
• 年卷期：v.8,no.1(January 18, 2013)
• ISSN：1554-8937

文摘

Over the past 15 years protein kinases have become the pharmaceutical industry鈥檚 most important class of drug target in the field of cancer. Some 20 drugs that target kinases have been approved for clinical use over the past decade, and hundreds more are undergoing clinical trials. However, the recent approval of the first protein kinase inhibitors for the treatment of inflammatory diseases, coupled with an enhanced understanding of the signaling networks that control the immune system, suggests that there will be a surge of interest in this area over the next 10 years. In this connection, we discuss opportunities for targeting protein kinases in the MyD88 signaling network for the development of drugs to treat chronic inflammatory and autoimmune diseases. Activating mutations in protein kinases underlie many other diseases and conditions, and we also discuss why the protein kinases SPAK/OSR1 and LRRK2 have recently become interesting targets for the treatment of hypertension and Parkinson鈥檚 disease, respectively, and the progress that has been made in developing LRRK2 inhibitors. Finally we suggest that more focus on the identification of inhibitors of kinase activation, rather than kinase activity, may pay dividends in identifying exquisitely specific inhibitors of signal transduction cascades, and we also highlight 鈥減seudo-kinases鈥?as an attractive and unexplored area for drug development that merits much more attention in the years to come.