摘要
弥漫性内源性脑桥胶质瘤(DIPG)主要影响中位年龄为6-7岁的儿童。占所有儿童肿瘤的10%。不幸的是,DIPG预后较差,中位生存期一般小于16-24个月,独立于所接受的治疗。到目前为止,患有DIPG的儿童只能接受局部放疗或联合抗肿瘤药物治疗。在过去的十年里,ONC201被称为多巴胺受体拮抗剂,通过对公共化合物库的高通量筛选,被发现具有对几种癌细胞株的细胞毒活性。努力确定真正的ONC201目标,负责其抗扩散效果。假设的靶点是肿瘤坏死因子相关凋亡诱导配体刺激(TRAIL),靶向相同肿瘤抑制基因(FOXO3a)的两种致癌激酶(ERK/AKT系统),多巴胺受体(DRD2和DRD3亚型),最后是线粒体Caseynolitic蛋白酶P (ClpP)。ONC201综述,讨论了结构与活性关系与其他两类化合物,即动物脂肪和D9,已知的抗生素活性,但值得注意的是讨论和研究作为潜在的“领导”发展的新药物用于治疗DIPG。在这篇综述中,我们对ONC201、ADEPs和D9促凋亡活性进行了详细和关键的描述,并特别关注了其与靶标建立的特定相互作用。文献来源为Pubmed近十年发表的专利和临床试验报告。
关键词: 弥漫性内在脑桥胶质瘤(DIPG), ONC201
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