以G-四螺旋为靶点的抗肿瘤药物研究进展

端粒酶的表达可见于大多数肿瘤细胞,而正常体细胞均无端粒酶的表达,表明端粒酶可能是一个很好的肿瘤治疗靶点.端粒末端DNA形成G-四螺旋,能阻止端粒酶发挥功能,抑制端粒酶活性,另外在一些癌基因的启动子区域也可形成G-四螺旋,控制癌基因.已经发现多种小分子化合物可以诱导和稳定G-四螺旋的结构.这些小分子化合物有强大的端粒酶活性抑制和诱导肿瘤细胞快速衰老的作用,靶向G-四螺旋提供了新颖的广谱的抗肿瘤治疗策略.

Research Progress of Targeting G-quadruplex Anticancer Agents

Telomerase activity is expressed in most types of cancer cells but not in normal somatic cells,suggesting that telomerase may be an important target for cancer chemotherapy.Telomeric DNA formats G-quadruplex,thereby inhibits telomerase activity,Also,formation of G-quadruplex in promoters of several oncogenes can inhibit expression of oncogenes,Several classes of small molecules have been described to induce the G-rich single-stranded overhang of telomeric DNA to fold into 4-stranded Gvquadruplex structures,These molecules have shown potent telomerase inhibition and the rapid induction of senescence in cancer cells.Targeting the G-quadruplex machinery offers a novel and potentially broad-spectrum anticancer therapeutic strategy.