Currently, as the largest family of E3 ubiquitin ligases, Skp1-Cullin 1-F-box (SCF) E3 ligase complexes have attracted extensive attention. Among SCF complexes, Skp2, β-TrCP, and FBXW7 have undergone extensive research on their structures and functions. Previous studies suggest Skp2, β-TrCP, and FBXW7 are overexpressed in numerous cancers. Thus, the SCF E3 ligase complex has become a significant target for the development of anti-cancer drugs. Over the past few decades, a variety of anti-tumor inhibitors targeting the SCF E3 ligase complex have been attempted. However, since almost none of the SCF E3 ligase inhibitors passed clinical trials, the design and synthesis of the new inhibitors are needed. Here, we will introduce the structure and function of Skp2, β-TrCP, and FBXW7, their connections with cancer development, the relevant in vitro and in vivo activities, selectivity, structure-activity relationships, and the therapeutic or preventive application of small molecule inhibitors targeting these three F-box proteins reported in the patent (2010–present). This information will help develop drugs targeting the SCF E3 ubiquitin ligase, providing new strategies for future cancer treatments.

中文翻译：

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SCF E3连接酶癌症抑制剂专利审查：结构设计、药理活性及构效关系


目前，作为最大的E3泛素连接酶家族，Skp1-Cullin 1-F-box (SCF) E3连接酶复合物引起了广泛的关注。在SCF复合物中，Skp2、β-TrCP和FBXW7对其结构和功能进行了广泛的研究。先前的研究表明 Skp2、β-TrCP 和 FBXW7 在多种癌症中过度表达。因此，SCF E3连接酶复合物已成为抗癌药物开发的重要靶点。在过去的几十年里，人们尝试了多种针对 SCF E3 连接酶复合物的抗肿瘤抑制剂。然而，由于几乎没有SCF E3连接酶抑制剂通过临床试验，因此需要设计和合成新的抑制剂。在此，我们将介绍Skp2、β-TrCP和FBXW7的结构和功能、它们与癌症发生发展的关系、相关的体内外活性、选择性、构效关系以及小分子的治疗或预防应用。专利（2010 年至今）中报道了针对这三种 F-box 蛋白的抑制剂。这些信息将有助于开发针对 SCF E3 泛素连接酶的药物，为未来的癌症治疗提供新策略。