Gakushuin University, Department of Chemistry, Faculty of Science, 1-5-1, Mejiro, Toshima-ku, Tokyo, 171-8588, Japan.
Expert Opin Ther Pat. 2011 Feb;21(2):131-46. doi: 10.1517/13543776.2011.547477. Epub 2011 Jan 6.
Hypoxia-inducible factor (HIF) is a heterodimeric transcription factor consisting of α and β subunits that regulates the expression of angiogenic factors, including VEGF, which are involved in angiogenesis, invasion/metastasis, glucose uptake and cell survival during cancer development.
This review summarizes the information about patented HIF inhibitors over the last 7 years (2004 - 2010). The reader will gain an outline of the structure and biological activity of recently developed HIF inhibitors.
Inhibition of HIF is an attractive therapeutic target for tumor angiogenesis and, until now, various HIF inhibitors have been discovered and evaluated. It is expected that development of more potent and selective HIF inhibitors will provide an effective treatment of cancer and other HIF-related diseases, including inflammation and cardiovascular disorder. As VEGF plays an important role in angiogenesis during tumor growth and ischemic diseases, the inhibition of VEGF-induced HIF is an attractive approach for the suppression of hypoxia-mediated pathological angiogenesis. HIF inhibitors may not only have cytostatic antitumor effects with fewer side effects, but also synergetic effects combined with radiotherapy.
缺氧诱导因子（HIF）是一种异二聚体转录因子，由α和β亚基组成，调节血管生成因子的表达，包括 VEGF，VEGF 参与血管生成、侵袭/转移、葡萄糖摄取和细胞存活在癌症发展过程中。
本文综述了过去 7 年（2004-2010 年）专利 HIF 抑制剂的信息。读者将对最近开发的 HIF 抑制剂的结构和生物学活性有一个概述。
抑制 HIF 是肿瘤血管生成的一个有吸引力的治疗靶点，到目前为止，已经发现并评估了各种 HIF 抑制剂。预计开发更有效和选择性的 HIF 抑制剂将为癌症和其他 HIF 相关疾病（包括炎症和心血管疾病）提供有效的治疗方法。由于 VEGF 在肿瘤生长和缺血性疾病期间的血管生成中起重要作用，抑制 VEGF 诱导的 HIF 是抑制缺氧介导的病理性血管生成的一种有吸引力的方法。HIF 抑制剂不仅可能具有较少副作用的细胞增殖抑制抗肿瘤作用，而且还可能与放疗具有协同作用。
