Identifying Small Molecules that Bind to the Cbl-b E3-Ligase

识别与 Cbl-b E3-连接酶结合的小分子

• 批准号: 2750375
• 金额: --
• 依托单位: Institute of Cancer Research
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2750375
• 关键词: Identifying; Small; Molecules; Bind; Cbl

The Casitas B-lineage E3 ligases are a family of closely related RING-type, mono-subunit E3 ligases (c-Cbl, Cbl-b, Cbl3) which play important roles in the regulation of tyrosine kinases. Cbl-b has attracted particular interest as it has been shown to be a key check-point regulator of both the innate and adaptive immune system and mice lacking Cblb have demonstrated enhanced T-cell killing and spontaneous rejection of tumours. Small molecules that bind to Cblb may therefore act as novel immune checkpoint regulators. Furthermore, as Cbl-b is an E3 ligase they could also serve as the basis for generating novel, alternative PROTACs.

Casitas B-谱系E3连接酶是密切相关的RING型单亚基E3连接酶（c-Cbl、Cbl-b、Cbl 3）的家族，其在酪氨酸激酶的调节中起重要作用。Cbl-b已经引起了特别的兴趣，因为它已被证明是先天性和适应性免疫系统的关键检查点调节剂，并且缺乏Cblb的小鼠已经证明了增强的T细胞杀伤和肿瘤的自发排斥。因此，与Cblb结合的小分子可以作为新的免疫检查点调节剂。此外，由于Cbl-b是一种E3连接酶，它们也可以作为产生新的替代PROTAC的基础。