Identification of Potent and Selective Amidobipyridyl Inhibitors of Protein Kinase D

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• 作者：Erik L. Meredith ; Kimberly Beattie ; Robin Burgis ; Michael Capparelli ; Joseph Chapo ; Lucian DiPietro ; Gabriel Gamber ; Istvan Enyedy ; David B. Hood ; Vinayak Hosagrahara ; Charles Jewell ; Keith A. Koch ; W
• 刊名：Journal of Medicinal Chemistry
• 出版年：2010
• 出版时间：August 12, 2010
• 年：2010
• 卷：53
• 期：15
• 页码：5422-5438
• 全文大小：1199K
• 年卷期：v.53,no.15(August 12, 2010)
• ISSN：1520-4804

文摘

The synthesis and biological evaluation of potent and selective PKD inhibitors are described herein. The compounds described in the present study selectively inhibit PKD among other putative HDAC kinases. The PKD inhibitors of the present study blunt phosphorylation and subsequent nuclear export of HDAC4/5 in response to diverse agonists. These compounds further establish the central role of PKD as an HDAC4/5 kinase and enhance the current understanding of cardiac myocyte signal transduction. The in vivo efficacy of a representative example compound on heart morphology is reported herein.