BH3類似物促細(xì)胞凋亡機(jī)制及臨床研究進(jìn)展
發(fā)布時(shí)間：2018-10-16 16:34
【摘要】：靶向細(xì)胞凋亡是目前癌癥治療中最具發(fā)展前景的治療方法之一。BCL-2家族的BH3-only蛋白(僅含BCL-2同源結(jié)構(gòu)域BH3)可以通過(guò)與家族中促存活蛋白結(jié)合,使促存活蛋白失效,從而使促凋亡成員發(fā)揮作用,最終導(dǎo)致細(xì)胞發(fā)生程序性凋亡。BH3類似物即一類可以模仿BH3-only蛋白并誘發(fā)細(xì)胞凋亡的小分子化合物。BH3類似物的原型ABT-737可以選擇性靶向BCL-XL、BCL-2和BCL-W 3個(gè)促存活蛋白(但不能作用于髓細(xì)胞白血病因子-1蛋白或A1蛋白),而它的衍生物ABT-263(navitoclax)在臨床試驗(yàn)中有顯著的促凋亡與抗腫瘤效應(yīng)�，F(xiàn)階段,一些推測(cè)為BH3類似物的藥物已經(jīng)進(jìn)入了臨床階段,但很大一部分仍在進(jìn)行特征鑒定。本文在概述BH3-only蛋白作用機(jī)制的基礎(chǔ)上,綜述了多種已經(jīng)廣泛認(rèn)可的BH3類似物及正在研究當(dāng)中的最新BH3類似物。
[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.
【作者單位】： 北京大學(xué)醫(yī)學(xué)部基礎(chǔ)醫(yī)學(xué)院藥理學(xué)系;
【基金】：國(guó)家自然科學(xué)基金(81673453);國(guó)家自然科學(xué)基金(81473235);國(guó)家自然科學(xué)基金(91129727) 教育部111項(xiàng)目(B07001)~~
【分類號(hào)】：R96
本文編號(hào)：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.
【作者單位】： 北京大學(xué)醫(yī)學(xué)部基礎(chǔ)醫(yī)學(xué)院藥理學(xué)系;
【基金】：國(guó)家自然科學(xué)基金(81673453);國(guó)家自然科學(xué)基金(81473235);國(guó)家自然科學(xué)基金(91129727) 教育部111項(xiàng)目(B07001)~~
【分類號(hào)】：R96
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