PNAS:小分子选择性诱导脑癌凋亡

2019-03-10 海北 MedSci原创

最近,研究人员从基于细胞的化学筛选中鉴定出了一种小分子,称为RIPGBM。该筛选在多个原发性患者来源的GBM CSC培养物中选择性诱导细胞凋亡。

多形性胶质母细胞瘤(GBM; IV级星形细胞瘤)是最常见和最具侵袭性的原发性脑癌形式。被称为GBM癌症干细胞CSC)的多能细胞亚群在肿瘤起始,肿瘤维持,转移,耐药性和手术后复发中起关键作用。

最近,研究人员从基于细胞的化学筛选中鉴定出了一种小分子,称为RIPGBM。该筛选在多个原发性患者来源的GBM CSC培养物中选择性诱导细胞凋亡。

该化合物的细胞类型依赖性选择性似乎部分源于GBM CSC中被称为cRIPGBM的促凋亡衍生物的氧化还原依赖性形成。 cRIPGBM通过与受体相互作用蛋白激酶2RIPK2)结合,并作为分子开关诱导胱天蛋白酶1依赖性细胞凋亡,其减少促存活的RIPK2 / TAK1复合物的形成,并增加促凋亡RIPK2 /半胱天冬酶1复合物的形成。

在原位颅内GBM CSC肿瘤异种移植小鼠模型中,研究人员发现RIPGBM显着抑制体内肿瘤形成。

因此,这个基于化学遗传学的方法帮助确定了候选药物和潜在的药物靶标,为这种破坏性疾病的治疗提供了一种潜在的方法。


原始出处:

Lucki NC et al. A cell type-selective apoptosis-inducing small molecule for the treatment of brain cancer. PNAS, 2019; doi: 10.1073/pnas.1816626116.


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    2019-10-20 宋威
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    2019-07-09 drwjr
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    2019-03-19 Dr.ZHS

    原文走起。

    0

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