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摘要
肿瘤血管生成一直是有效的癌症治疗的一个主要的裂口。异常的血管生成抑制剂靶向受体酪氨酸激酶(RTK)中断了药物化学家的巨大兴趣。在参与肿瘤血管生成因子中,血管内皮生长因子受体-2(VEGFR-2)确认为最密切相关的因素使血管通过结合其天然配体血管内皮生长因子。很好的验证血管内皮生长因子驱动的血管内皮生长因子受体-2信号通路能刺激多种内皮细胞的反应,包括增加血管通透性,促进内皮细胞增殖、迁移和分化。因此,通过血管内皮生长因子受体-2抑制剂的血管生成是规避对抗各种血管内皮生长因子受体-2介导疾病以及耐药性的一种策略。在过去的几十年中,有相当数量的新的小分子血管内皮生长因子受体抑制剂已与不同的化学材料的开发。特别是最近频繁推出的抑制剂已经宣布他们的研究价值和治疗潜力在肿瘤。然而,抗血管生成的治疗仍然是一个持续的挑战。本文全面回顾新出现的血管内皮生长因子受体-2抑制剂的研究现状进行了综述,对构效关系(SAR)重点调查,并结合模式与生物靶代表抑制剂。在所有这些信息的基础上,制定强有力的血管内皮生长因子受体-2抑制剂不同策略和抗血管生成抑制剂的临床应用前景在此进行了讨论。
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。
Current Medicinal Chemistry
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.
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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
DOI https://dx.doi.org/10.2174/0929867323666160210130426 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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