BH3类似物促细胞凋亡机制及临床研究进展
发布时间：2018-10-16 16:34
【摘要】：靶向细胞凋亡是目前癌症治疗中最具发展前景的治疗方法之一。BCL-2家族的BH3-only蛋白(仅含BCL-2同源结构域BH3)可以通过与家族中促存活蛋白结合,使促存活蛋白失效,从而使促凋亡成员发挥作用,最终导致细胞发生程序性凋亡。BH3类似物即一类可以模仿BH3-only蛋白并诱发细胞凋亡的小分子化合物。BH3类似物的原型ABT-737可以选择性靶向BCL-XL、BCL-2和BCL-W 3个促存活蛋白(但不能作用于髓细胞白血病因子-1蛋白或A1蛋白),而它的衍生物ABT-263(navitoclax)在临床试验中有显著的促凋亡与抗肿瘤效应。现阶段,一些推测为BH3类似物的药物已经进入了临床阶段,但很大一部分仍在进行特征鉴定。本文在概述BH3-only蛋白作用机制的基础上,综述了多种已经广泛认可的BH3类似物及正在研究当中的最新BH3类似物。
[Abstract]:Targeted apoptosis is one of the most promising therapies for cancer treatment. BH3-only proteins (including only BCL-2 homologous domain BH3) of the BCL-2 family can make survivin proteins ineffective by binding to survivin in the family. In order to make apoptotic members play a role, BH3 analogue is a class of small molecular compounds that mimic BH3-only protein and induce cell apoptosis. The prototype ABT-737 of BH3 analogue can selectively target BCL-XL,BCL-2 and BCL-W three pro-survival proteins (but cannot It acts on myeloid leukemia factor-1 protein or A1 protein, and its derivative, ABT-263 (navitoclax), has significant apoptotic and anti-tumor effects in clinical trials. At this stage, some drugs that are presumed to be BH3 analogues have entered the clinical stage, but a large part of them are still in the process of characterization. On the basis of summarizing the mechanism of action of BH3-only protein, this paper reviews several widely recognized BH3 analogues and the latest BH3 analogues under study.
【作者单位】： 北京大学医学部基础医学院药理学系;
【基金】：国家自然科学基金(81673453);国家自然科学基金(81473235);国家自然科学基金(91129727) 教育部111项目(B07001)~~
【分类号】：R96
本文编号：2274987
[Abstract]:Targeted apoptosis is one of the most promising therapies for cancer treatment. BH3-only proteins (including only BCL-2 homologous domain BH3) of the BCL-2 family can make survivin proteins ineffective by binding to survivin in the family. In order to make apoptotic members play a role, BH3 analogue is a class of small molecular compounds that mimic BH3-only protein and induce cell apoptosis. The prototype ABT-737 of BH3 analogue can selectively target BCL-XL,BCL-2 and BCL-W three pro-survival proteins (but cannot It acts on myeloid leukemia factor-1 protein or A1 protein, and its derivative, ABT-263 (navitoclax), has significant apoptotic and anti-tumor effects in clinical trials. At this stage, some drugs that are presumed to be BH3 analogues have entered the clinical stage, but a large part of them are still in the process of characterization. On the basis of summarizing the mechanism of action of BH3-only protein, this paper reviews several widely recognized BH3 analogues and the latest BH3 analogues under study.
【作者单位】： 北京大学医学部基础医学院药理学系;
【基金】：国家自然科学基金(81673453);国家自然科学基金(81473235);国家自然科学基金(91129727) 教育部111项目(B07001)~~
【分类号】：R96
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