【摘要】 肿瘤的缺氧微环境与其增殖、分化、血管生成、能量代谢、耐药性的发生以及患者预后状况密切相关。缺氧诱导因子1(Hypoxia-inducible factor 1, HIF-1)是细胞适应缺氧环境的重要转录因子和调控蛋白,通过调控下游靶基因如EPO、VEGF、GLUT等的表达,促进血管新生及有氧糖酵解以适应缺氧的环境,进而影响肿瘤细胞代谢、血管生成和肿瘤转移等。因此,开发以HIF-1为靶标的小分子抑制剂药物有望成为一种有效的肿瘤治疗方法。本文就HIF-1小分子抑制剂在肿瘤学研究中的进展进行综述,旨在为靶向HIF-1抗肿瘤药物的研发提供新思路。更多还原

【Abstract】 Tumor hypoxia is associated with tumor proliferation, differentiation, angiogenesis and energy metabolism. It has been found that hypoxia induces chemoresistance and poor prognosis in varieties of solid tumors. Hypoxia-inducible factor 1(HIF-1) is an important transcription factor and regulator for inducing cells to adapt to hypoxia or anoxia environment. By regulating the expression of downstream targets such as EPO, VEGF, and GLUT, HIF-1 has been implicated in the activation of tumor glycolysis, angiogenesis and metastasis. Therefore, the discovery and development of small molecule inhibitors targeting HIF-1 may potentially lead to new chemotherapy for cancer treatment. In this review, we summarize the current state of the art and recent progress in the development of HIF-1 small molecule inhibitors, which may provide new insights into the design and discovery of HIF-1 targeted innovational drugs.更多还原