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缺氧诱导因子-1α(hypoxia-inducible factor-1α,HIF-1α)在缺氧肿瘤细胞尤其是实体瘤中都存在着过度表达,它能够控制下游100多种基因的表达,包括血管内皮生长因子(VEGF)、葡萄糖转移酶-1(GLUT-1)、酪氨酸激酶(c-Met)等,对肿瘤细胞的增殖、转移、侵入、凋亡以及糖代谢都有至关重要的作用。已经证明许多已经上市的和进入临床研究的药物都具有HIF-1α抑制活性。近几年,设计合成的多种类型的新型小分子HIF-1抑制剂,有望成为新一类抗肿瘤药物。本文主要对近年来设计合成的新型HIF-1α抑制剂进行综述。
Hypoxia-inducible factor-1α (HIF-1α) is overexpressed in hypoxic tumor cells, especially in solid tumors. It controls the expression of more than 100 downstream genes, including vascular endothelial growth factor VEGF, GLUT-1 and c-Met, play an important role in the proliferation, metastasis, invasion, apoptosis and glucose metabolism of tumor cells. Many drugs already on the market and in clinical trials have demonstrated HIF-1α inhibitory activity. In recent years, the design and synthesis of many types of new small molecule HIF-1 inhibitors, is expected to become a new class of anti-tumor drugs. This review summarizes the novel HIF-1α inhibitors designed and synthesized in recent years.