Focal adhesion kinase (FAK) promotes tumor progression by intracellular signal transduction and regulation of gene expression and protein turnover, which is a compelling therapeutic target for various cancer types, including ovarian cancer. However, the clinical responses of FAK inhibitors remain unsatisfactory. Here, we describe the discovery of FAK inhibitors using a scaffold hopping strategy. Structure–activity relationship (SAR) exploration identified 36 as a potent FAK inhibitor, which exhibited inhibitory activities against FAK signaling in vitro. Treatment with 36 not only decreased migration and invasion of PA-1 cells, but also reduced expression of MMP-2 and MMP-9. Moreover, 36 inhibited tumor growth and metastasis, and no obvious adverse effects were observed during the in vivo study. These results revealed the potential of FAK inhibitor 36 for treatment of ovarian cancer.

粘着斑激酶 (FAK) 通过细胞内信号转导和基因表达和蛋白质转换的调节促进肿瘤进展，这是包括卵巢癌在内的各种癌症类型的引人注目的治疗靶点。然而，FAK抑制剂的临床反应仍然不能令人满意。在这里，我们描述了使用支架跳跃策略发现 FAK 抑制剂。构效关系 (SAR) 探索确定36是一种有效的 FAK 抑制剂，在体外表现出对 FAK 信号传导的抑制活性。用36处理不仅减少了 PA-1 细胞的迁移和侵袭，而且还减少了 MMP-2 和 MMP-9 的表达。此外，36抑制肿瘤生长和转移，体内研究未见明显不良反应。这些结果揭示了 FAK 抑制剂36治疗卵巢癌的潜力。