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酸性神经酰胺酶抑制剂的研究进展
Progress in the studies on acid ceramidase inhibitors
【摘要】 酸性神经酰胺酶(acid ceramidase,AC)是位于溶酶体内的神经酰胺(ceramide,Cer)代谢酶,能够调节神经酰胺(Cer)/鞘氨醇(sphingosine,Sph)/1-磷酸鞘氨醇(sphingosine1-phosphate,S1P)之间的相互代谢平衡。而Cer和S1P已被公认是调控细胞生长、增殖和死亡的重要信号分子,AC的过量表达,可使S1P水平升高,产生抗细胞凋亡效应。因此,AC有希望成为癌症治疗的全新靶点之一,通过抑制AC活性,诱导肿瘤细胞凋亡,为癌症治疗提供了新思路。本文对近年来AC抑制剂的研究进展进行综述。
【Abstract】 Acid ceramidase(AC) is a metabolic enzyme of ceramide(Cer) that is located in lysosome,AC consists of 395 amino acids.Its activity is best when p H is between 4.0 and 5.0.It can regulate the balance of Cer-Sphingosine(Sph)-Sphingosine1-phosphate(S1P) inter-metabolism.Cer and S1 P are increasingly recognized for their important roles as signaling molecules involved in regulation of survival,proliferation and cell death.The overexpression of AC leads to the effect of anti-apoptosis.Besides,AC has been confirmed that it overexpresses in prostate cancer,melanoma and so on.So,AC has been a newtarget for cancer therapy,and inhibiting the activity of AC can induce the apoptosis of tumour cells,it can provide a newsight of cancer therapy.This reviewmainly describes the recent developments of AC inhibitors.
【Key words】 acid ceramidase; acid ceramidase inhibitors; structure-activity relationship;
- 【文献出处】 中国药物化学杂志 ,Chinese Journal of Medicinal Chemistry , 编辑部邮箱 ,2016年06期
- 【分类号】R979.1
- 【被引频次】3
- 【下载频次】386