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Identification of Potent and Selective Amidobipyridyl Inhibitors of Protein Kinase D

  作者 MEREDITH ERIK L; BEATTIE KIMBERLY; BURGIS ROBIN; CAPPARELLI MICHAEL; CHAPO JOSEPH; DIPIETRO LUCIAN; GAMBER GABRIEL; ENYEDY ISTVAN; HOOD DAVID B; HOSAGRAHARA VINAYAK; JEWELL CHARLES; KOCH KEITH A; LEE WENDY; LEMON DOUGLAS D; MCKINSEY TIMOTHY A; MIRANDA KARL; PAGRATIS NIKOS; PHAN DILLON; PLATO CRAIG; RAO CHANG; ROZHITSKAYA OLGA; SOLDERMANN NICOLAS; SPRINGER CLAYTON; VAN EIS MAURICE; VEGA RICHARD B; YAN WANLIN; ZHU QINGMING; MONOVICH LAUREN G  
  选自 期刊  Journal of Medicinal Chemistry;  卷期  2010年53-15;  页码  5422-5438  
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[摘要]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.

 
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