Targeting Cullin-RING E3 Ubiquitin Ligase 4 by Small Molecule Modulators.
Targeting Cullin-RING E3 Ubiquitin Ligase 4 by Small Molecule Modulators.
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DOI：
10.33696/signaling.2.051
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Pan ZQ
中科院分区：
文献类型：
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作者：
Wu K;Hopkins BD;Sanchez R;DeVita RJ;Pan ZQ
Cullin-RING E3 泛素连接酶 4 (CRL4) 在细胞周期进程中发挥重要作用。最近使用高通量筛选和后续的先导化合物研究已鉴定出小分子 33-11 和 KH-4-43，它们可抑制 E3 CRL4 的核心连接酶复合物并表现出抗癌潜力。本综述提供：1）E3 CRL4 的最新观点，包括结构组织、主要底物靶点和在癌症中的作用； 2）讨论寻找CRL抑制剂的挑战和策略； 3) 已鉴定的 CRL4 抑制剂的特性总结，以及对其探索 CRL4 生物学和作为治疗剂的潜在用途的展望。
Cullin-RING E3 ubiquitin ligase 4 (CRL4) plays an essential role in cell cycle progression. Recent efforts using high throughput screening and follow up hit-to-lead studies have led to identification of small molecules 33-11 and KH-4-43 that inhibit E3 CRL4’s core ligase complex and exhibit anticancer potential. This review provides: 1) an updated perspective of E3 CRL4, including structural organization, major substrate targets and role in cancer; 2) a discussion of the challenges and strategies for finding the CRL inhibitor; and 3) a summary of the properties of the identified CRL4 inhibitors as well as a perspective on their potential utility to probe CRL4 biology and act as therapeutic agents.