摘要
粘着斑激酶 (FAK) 是一种非受体酪氨酸激酶,参与细胞增殖、存活、迁移和侵袭过程。由于其在多种癌症类型中的过度表达和/或激活,它已成为治疗人类转移性癌症的有希望的治疗靶点。由于 FAK 因其在癌症中的转录和翻译水平的过度表达而成为潜在的癌症靶点,因此在过去几年中发现了具有多样化支架的不同类型的 FAK 抑制剂。本文综述了近期发现的小分子FAK抑制剂的研究进展。主要的努力集中在小分子FAK抑制剂的合理设计和合成上,并且还讨论了它们的构效关系(SAR)分析。其中,虽然 I 型抑制剂仍然是主要焦点,但 II 型抑制剂和新型变构 FAK 抑制剂(III 型抑制剂)已被开发以提高效力和选择性。同时,还发现了新的策略,例如使用蛋白质-蛋白质相互作用的抑制剂靶向 FAK。最后,提供了一些关于 FAK 抑制剂作为抗癌疗法的未来发展的见解和观点。
关键词: 抗癌疗法、癌症靶点、药物设计、粘着斑激酶 (FAK)、小分子 FAK 抑制剂、构效关系 (SAR) 分析。
Current Medicinal Chemistry
Title:Recent Advances of Small Molecule Focal Adhesion Kinase (FAK) Inhibitors as Promising Anticancer Therapeutics
Volume: 28 Issue: 34
关键词: 抗癌疗法、癌症靶点、药物设计、粘着斑激酶 (FAK)、小分子 FAK 抑制剂、构效关系 (SAR) 分析。
摘要: Focal Adhesion Kinase (FAK) is a non-receptor tyrosine kinase involved in the process of cell proliferation, survival, migration, and invasion. It has become a promising therapeutic target for the treatment of human metastatic cancers due to its overexpression and/or activation in multiple cancer types. Since FAK is emerging as a potential cancer target because of its overexpression at both the transcriptional and translational level in cancer, different types of FAK inhibitors with diversified scaffolds have been discovered in the past few years. In this review, the progress of recently discovered small molecule FAK inhibitors was summarized. Major efforts have been focused on the rational design and synthesis of small molecule FAK inhibitors, and their structure-activity relationship (SAR) analysis wasalso discussed. Among them, while type I inhibitors remain as the major focuses, type II inhibitors and novel allosteric FAK inhibitors (type III inhibitors) have been developed to improve both potency and selectivity. Meanwhile, novel strategies, such as targeting FAK using inhibitors of protein-protein interactions, were also discovered. Lastly, some insights and perspectives on the future development of FAK inhibitors as anticancer therapeutics have been provided.
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Cite this article as:
Recent Advances of Small Molecule Focal Adhesion Kinase (FAK) Inhibitors as Promising Anticancer Therapeutics, Current Medicinal Chemistry 2021; 28 (34) . https://dx.doi.org/10.2174/0929867328666210331143827
DOI https://dx.doi.org/10.2174/0929867328666210331143827 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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