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靶向 Syk:脾酪氨酸激酶作为治疗靶点。

Getting Syk: spleen tyrosine kinase as a therapeutic target.

机构信息

Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, Hansen Life Sciences Research Building, 210 South University Street, West Lafayette, IN 47907, USA.

出版信息

Trends Pharmacol Sci. 2014 Aug;35(8):414-22. doi: 10.1016/j.tips.2014.05.007. Epub 2014 Jun 26.

DOI:10.1016/j.tips.2014.05.007
PMID:24975478
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4119858/
Abstract

Spleen tyrosine kinase (Syk) is a cytoplasmic protein tyrosine kinase well known for its ability to couple immune cell receptors to intracellular signaling pathways that regulate cellular responses to extracellular antigens and antigen-immunoglobulin (Ig) complexes of particular importance to the initiation of inflammatory responses. Thus, Syk is an attractive target for therapeutic kinase inhibitors designed to ameliorate the symptoms and consequences of acute and chronic inflammation. Its more recently recognized role as a promoter of cell survival in numerous cancer cell types ranging from leukemia to retinoblastoma has attracted considerable interest as a target for a new generation of anticancer drugs. This review discusses the biological processes in which Syk participates that have made this kinase such a compelling drug target.

摘要

脾酪氨酸激酶(Syk)是一种细胞质蛋白酪氨酸激酶,以其能够将免疫细胞受体与细胞内信号通路偶联的能力而闻名,这些信号通路调节细胞对外源抗原和抗原-免疫球蛋白(Ig)复合物的反应,这对于启动炎症反应尤为重要。因此,Syk 是治疗性激酶抑制剂的一个有吸引力的靶点,旨在改善急性和慢性炎症的症状和后果。其最近被认为在从白血病到视网膜母细胞瘤的多种癌细胞类型中作为促进细胞存活的促进因子,这使其成为新一代抗癌药物的一个有吸引力的靶点。本文综述了 Syk 参与的生物学过程,这些过程使这种激酶成为一个引人注目的药物靶点。

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Trends Pharmacol Sci. 2014 Aug;35(8):414-22. doi: 10.1016/j.tips.2014.05.007. Epub 2014 Jun 26.
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本文引用的文献

1
A potential therapeutic strategy for chronic lymphocytic leukemia by combining Idelalisib and GS-9973, a novel spleen tyrosine kinase (Syk) inhibitor.一种通过联合使用idelalisib和新型脾酪氨酸激酶(Syk)抑制剂GS-9973治疗慢性淋巴细胞白血病的潜在治疗策略。
Oncotarget. 2014 Feb 28;5(4):908-15. doi: 10.18632/oncotarget.1484.
2
SYK is a critical regulator of FLT3 in acute myeloid leukemia.SYK 是急性髓系白血病中 FLT3 的关键调节因子。
Cancer Cell. 2014 Feb 10;25(2):226-42. doi: 10.1016/j.ccr.2014.01.022.
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SYK allelic loss and the role of Syk-regulated genes in breast cancer survival.SYK等位基因缺失以及Syk调控基因在乳腺癌生存中的作用。
PLoS One. 2014 Feb 11;9(2):e87610. doi: 10.1371/journal.pone.0087610. eCollection 2014.
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B cell-specific loss of Lyn kinase leads to autoimmunity.B 细胞特异性 Lyn 激酶缺失导致自身免疫。
J Immunol. 2014 Feb 1;192(3):919-28. doi: 10.4049/jimmunol.1301979. Epub 2013 Dec 27.
5
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Arthritis Res Ther. 2013 Oct 4;15(5):R146. doi: 10.1186/ar4329.
6
Spleen tyrosine kinase (Syk) regulates systemic lupus erythematosus (SLE) T cell signaling.脾酪氨酸激酶(Syk)调节系统性红斑狼疮(SLE)T 细胞信号转导。
PLoS One. 2013 Aug 27;8(8):e74550. doi: 10.1371/journal.pone.0074550. eCollection 2013.
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Inhibitors of switch kinase 'spleen tyrosine kinase' in inflammation and immune-mediated disorders: a review.炎症和免疫介导性疾病中开关激酶“脾酪氨酸激酶”抑制剂:综述。
Eur J Med Chem. 2013 Sep;67:434-46. doi: 10.1016/j.ejmech.2013.04.070. Epub 2013 Jul 12.
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Toll-like receptor 4 mediates retinal ischemia/reperfusion injury through nuclear factor-κB and spleen tyrosine kinase activation.Toll 样受体 4 通过核因子-κB 和脾酪氨酸激酶的激活介导视网膜缺血/再灌注损伤。
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New insights into pre-BCR and BCR signalling with relevance to B cell malignancies.深入了解 pre-BCR 和 BCR 信号转导与 B 细胞恶性肿瘤的关系。
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