抗血管生成治疗：制定有效的血管内皮生长因子 及其受体-2酪氨酸激酶抑制剂和未来前景的策略

Title:Anti-Angiogenic Therapy: Strategies to Develop Potent VEGFR-2 Tyrosine Kinase Inhibitors and Future Prospect

Volume: 23 Issue: 10

Author(s): Leilei Shi, Jianfeng Zhou, Jifeng Wu, Yuemao Shen, Xun Li

Affiliation:

关键词: 血管内皮生长因子受体-2抑制剂，设计策略，对构效关系；药效，结合模式，抗血管生成。

摘要: Tumor angiogenesis has always been a major gap for effective cancer therapy. Interruption of aberrant angiogenesis by specific inhibitors targeting receptor tyrosine kinases (RTKs) has been of great interests to medicinal chemists. Among the factors that are involved in tumor angiogenesis, vascular endothelial growth factor receptor-2 (VEGFR-2) is validated as the most closely related factor which can drive angiogenesis through binding with its natural ligand VEGF. The well-validated VEGF-driven VEGFR-2 signaling pathway can stimulate many endothelial responses, including increasing vessel permeability and enhancing endothelial cell proliferation, migration and differentiation. Consequently, circumventing angiogenesis by VEGFR-2 inhibitors represents a promising strategy for counteracting various VEGFR-2-mediated disorders as well as drug resistance. Over the past decades, a considerable number of novel small molecular VEGFR-2 inhibitors have been exploited with diverse chemical scaffolds. Especially, recent frequently launched inhibitors have declared their research values and therapeutic potentials in oncology. Still, the antiangiogenesis based treatment remains an ongoing challenge. In this review, a comprehensive retrospective of newly emerged VEGFR-2 inhibitors have been summarized, with the emphasis on the structure-activity relationship (SAR) investigation, and also binding patterns of representative inhibitors with biotargets. On the basis of all of this information, varied strategies for developing potent VEGFR-2 inhibitors and the future prospect of the clinical application of antiangiogenic inhibitors are discussed hereby.

Cite this article as:

Leilei Shi, Jianfeng Zhou, Jifeng Wu, Yuemao Shen, Xun Li , Anti-Angiogenic Therapy: Strategies to Develop Potent VEGFR-2 Tyrosine Kinase Inhibitors and Future Prospect, Current Medicinal Chemistry 2016; 23 (10) . https://dx.doi.org/10.2174/0929867323666160210130426