...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>MedChemComm >Novel sphingosine-containing analogues selectively inhibit sphingosine kinase (SK) isozymes, induce SK1 proteasomal degradation and reduce DNA synthesis in human pulmonary arterial smooth muscle cells
【24h】

Novel sphingosine-containing analogues selectively inhibit sphingosine kinase (SK) isozymes, induce SK1 proteasomal degradation and reduce DNA synthesis in human pulmonary arterial smooth muscle cells

机译：新型含鞘氨醇的类似物选择性抑制人肺动脉平滑肌细胞中的鞘氨醇激酶（SK）同工酶，诱导SK1蛋白酶体降解并减少DNA合成

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Sphingosine 1-phosphate (S1P) is involved in hyper-proliferative diseases such as cancer and pulmonary arterial hypertension. We have synthesized inhibitors that are selective for the two isoforms of sphingosine kinase (SK1 and SK2) that catalyze the synthesis of S1P. A thiourea adduct of sphinganine (F02) is selective for SK2 whereas the 1-deoxysphinganines 55-21 and 77-7 are selective for SK1. (2S,3R)-1-Deoxysphinganine (55-21) induced the proteasomal degradation of SK1 in human pulmonary arterial smooth muscle cells and inhibited DNA synthesis, while the more potent SK1 inhibitors PF-543 and VPC96091 failed to inhibit DNA synthesis. These findings indicate that moderate potency inhibitors such as 55-21 are likely to have utility in unraveling the functions of SK1 in inflammatory and hyperproliferative disorders.
机译：1-磷酸鞘氨醇（S1P）与癌症和肺动脉高压等过度增殖性疾病有关。我们已经合成了对鞘氨醇激酶（SK1和SK2）的两种同工酶具有选择性的抑制剂，这些酶催化S1P的合成。鞘氨醇的硫脲加合物（F02）对SK2具有选择性，而1-脱氧鞘氨醇55-21和77-7对SK1具有选择性。 （2S，3R）-1-脱氧鞘氨醇（55-21）诱导人肺动脉平滑肌细胞中SK1的蛋白酶体降解并抑制DNA合成，而更有效的SK1抑制剂PF-543和VPC96091无法抑制DNA合成。这些发现表明中等效力的抑制剂如55-21可能在阐明SK1在炎性和过度增殖性疾病中的功能方面具有效用。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号