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Chem Commun (Camb). 2013 Mar 14;49(21):2136-8. doi: 10.1039/c3cc00181d. Epub 2013 Feb 7.
2
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3
FTY720 analogues as sphingosine kinase 1 inhibitors: enzyme inhibition kinetics, allosterism, proteasomal degradation, and actin rearrangement in MCF-7 breast cancer cells.FTY720 类似物作为鞘氨醇激酶 1 抑制剂：MCF-7 乳腺癌细胞中的酶抑制动力学、别构调节、蛋白酶体降解和肌动蛋白重排。
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Effect of alkyl chain length on sphingosine kinase 2 selectivity.烷基链长对鞘氨醇激酶 2 选择性的影响。
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Design, synthesis and biological activity of sphingosine kinase 2 selective inhibitors.鞘氨醇激酶 2 选择性抑制剂的设计、合成及生物活性。
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Discovery of novel sphingosine kinase 1 inhibitors.新型鞘氨醇激酶 1 抑制剂的发现。
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本文引用的文献

1
Modulation of cellular S1P levels with a novel, potent and specific inhibitor of sphingosine kinase-1.新型、强效且特异性的鞘氨醇激酶-1 抑制剂调节细胞 S1P 水平。
Biochem J. 2012 May 15;444(1):79-88. doi: 10.1042/BJ20111929.
2
Design, synthesis and biological activity of sphingosine kinase 2 selective inhibitors.鞘氨醇激酶 2 选择性抑制剂的设计、合成及生物活性。
Bioorg Med Chem. 2012 Jan 1;20(1):183-94. doi: 10.1016/j.bmc.2011.11.011. Epub 2011 Nov 15.
3
(R)-FTY720 methyl ether is a specific sphingosine kinase 2 inhibitor: Effect on sphingosine kinase 2 expression in HEK 293 cells and actin rearrangement and survival of MCF-7 breast cancer cells.(R)-FTY720 甲醚是一种特异性鞘氨醇激酶 2 抑制剂：对 HEK 293 细胞中鞘氨醇激酶 2 表达、肌动蛋白重排和 MCF-7 乳腺癌细胞存活的影响。
Cell Signal. 2011 Oct;23(10):1590-5. doi: 10.1016/j.cellsig.2011.05.010. Epub 2011 May 18.
4
FTY720 analogues as sphingosine kinase 1 inhibitors: enzyme inhibition kinetics, allosterism, proteasomal degradation, and actin rearrangement in MCF-7 breast cancer cells.FTY720 类似物作为鞘氨醇激酶 1 抑制剂：MCF-7 乳腺癌细胞中的酶抑制动力学、别构调节、蛋白酶体降解和肌动蛋白重排。
J Biol Chem. 2011 May 27;286(21):18633-40. doi: 10.1074/jbc.M111.220756. Epub 2011 Apr 4.
5
Sphingosine-1-phosphate produced by sphingosine kinase 2 in mitochondria interacts with prohibitin 2 to regulate complex IV assembly and respiration.线粒体中的鞘氨醇激酶 2 产生的鞘氨醇-1-磷酸与抑素 2 相互作用，调节复合物 IV 的组装和呼吸。
FASEB J. 2011 Feb;25(2):600-12. doi: 10.1096/fj.10-167502. Epub 2010 Oct 19.
6
SKI-II, an inhibitor of sphingosine kinase, ameliorates antigen-induced bronchial smooth muscle hyperresponsiveness, but not airway inflammation, in mice.SKI-II，一种鞘氨醇激酶抑制剂，可改善小鼠抗原诱导的支气管平滑肌高反应性，但不能改善气道炎症。
J Pharmacol Sci. 2010;114(3):304-10. doi: 10.1254/jphs.10202fp. Epub 2010 Oct 8.
7
The sphingosine kinase 1 inhibitor 2-(p-hydroxyanilino)-4-(p-chlorophenyl)thiazole induces proteasomal degradation of sphingosine kinase 1 in mammalian cells.鞘氨醇激酶 1 抑制剂 2-(对羟苯胺基)-4-(对氯苯基)噻唑诱导哺乳动物细胞中鞘氨醇激酶 1 的蛋白酶体降解。
J Biol Chem. 2010 Dec 10;285(50):38841-52. doi: 10.1074/jbc.M110.127993. Epub 2010 Oct 6.
8
Sphingosine-1-phosphate is a missing cofactor for the E3 ubiquitin ligase TRAF2.鞘氨醇-1-磷酸是 E3 泛素连接酶 TRAF2 的缺失辅因子。
Nature. 2010 Jun 24;465(7301):1084-8. doi: 10.1038/nature09128.
9
FTY720 and (S)-FTY720 vinylphosphonate inhibit sphingosine kinase 1 and promote its proteasomal degradation in human pulmonary artery smooth muscle, breast cancer and androgen-independent prostate cancer cells.FTY720 和（S）-FTY720 乙烯膦酸酯抑制人肺动脉平滑肌细胞、乳腺癌和雄激素非依赖性前列腺癌细胞中的鞘氨醇激酶 1 并促进其蛋白酶体降解。
Cell Signal. 2010 Oct;22(10):1536-42. doi: 10.1016/j.cellsig.2010.05.022. Epub 2010 Jun 4.
10
Sphingosine 1-phosphate and cancer.鞘氨醇 1-磷酸与癌症。
Nat Rev Cancer. 2010 Jul;10(7):489-503. doi: 10.1038/nrc2875. Epub 2010 Jun 17.

鞘氨醇激酶 1 选择性抑制剂的合成。

Synthesis of selective inhibitors of sphingosine kinase 1.

机构信息

Department of Chemistry and Biochemistry, Queens College of the City University of New York, Flushing, New York 11367-1597, USA.

出版信息

Chem Commun (Camb). 2013 Mar 14;49(21):2136-8. doi: 10.1039/c3cc00181d. Epub 2013 Feb 7.

DOI:10.1039/c3cc00181d
PMID:23388656
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3608193/
Abstract

Sphingosine kinase isoform 1 (SK1) inhibitors may serve as therapeutic agents for proliferative diseases, including hypertension. We synthesized a series of sphingosine-based SK1-selective inhibitors, the most potent of which is RB-005 (IC(50) = 3.6 μM), which also induced proteasomal degradation of SK1 in human pulmonary arterial smooth muscle cells.

摘要

鞘氨醇激酶同工型 1（SK1）抑制剂可能作为治疗增殖性疾病（包括高血压）的药物。我们合成了一系列基于鞘氨醇的 SK1 选择性抑制剂，其中最有效的是 RB-005（IC50=3.6μM），它还能诱导人肺动脉平滑肌细胞中 SK1 的蛋白酶体降解。