Identification of Potent and Selective Amidobipyridyl Inhibitors of Protein Kinase D
Identification of Potent and Selective Amidobipyridyl Inhibitors of Protein Kinase D
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DOI：
10.1021/jm100076w
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发表时间：
2010-08-12
影响因子：
7.3
通讯作者：
Monovich, Lauren G.
中科院分区：
文献类型：
--
作者：
Meredith, Erik L.;Beattie, Kimberly;Monovich, Lauren G.
本文描述了有效和选择性PKD抑制剂的合成和生物学评价。本研究中描述的化合物选择性抑制PKD以及其他推定的HDAC激酶。本研究的PKD抑制剂响应于多种激动剂而钝化HDAC 4/5的磷酸化和随后的核输出。这些化合物进一步确立了PKD作为HDAC 4/5激酶的中心作用，并增强了目前对心肌细胞信号转导的理解。本文报道了代表性实施例化合物对心脏形态的体内功效。
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.