Prospects for PLD Inhibition in Cancer and Thrombotic Disease.
Prospects for PLD Inhibition in Cancer and Thrombotic Disease.
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DOI：
10.1007/164_2019_244
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发表时间：
2019-09
影响因子：
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通讯作者：
Christian Salazar;M. Frohman
中科院分区：
文献类型：
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作者：
Christian Salazar;M. Frohman
磷脂酶D_1和磷脂酶D_2(PLD_1和PLD_2)是哺乳动物中PLD超家族的典型亚型，二十年来，人们利用细胞生物学和动物疾病模型研究了它们的功能。PLD1和PLD2在细胞外信号转导事件中被激活，并产生第二信使，信号转导脂质磷脂酸(PA)，已报道在从血小板激活到对心脏缺血、病毒感染、神经退行性疾病和癌症的反应中发挥作用。其中，最容易治疗的靶点可能是血栓性疾病和癌症，这里将在正在努力开发小分子PLD抑制剂的背景下讨论这一点。
Functions for phospholipase D1 and D2 (PLD1 and PLD2), the canonical isoforms of the PLD superfamily in mammals, have been explored using cell biological and animal disease models for two decades. PLD1 and PLD2, which are activated as a consequence of extracellular signaling events and generate the second messenger signaling lipid phosphatidic acid (PA), have been reported to play roles in settings ranging from platelet activation to the response to cardiac ischemia, viral infection, neurodegenerative disease, and cancer. Of these, the most tractable as therapeutic targets may be thrombotic disease and cancer, as will be discussed here in the context of ongoing efforts to develop small molecule PLD inhibitors.