Proteolysis targeting chimeras (PROTACs), which hijack proteins of interest (POIs) and recruit E3 ligases for target degradation via the ubiquitin-proteasome pathway, are a novel drug discovery paradigm that has been widely used as biological tools and medicinal molecules with the potential of clinical application value. To date, a wide variety of small molecule PROTACs have been developed. Importantly, VHL-based PROTACs have emerged to be a promising approach for proteins, including those non-druggable ones, such as transcriptional factors and scaffold proteins. VHL-based PRTOACs have been developed for the treatment of diseases that are difficult to be dealt with by conventional methods, such as radiotherapy, chemotherapy, and small molecule inhibitors. In this review, the recent advances of VHL-based PRTOACs were summarized, and the chances and challenges associated with this area were also highlighted.

蛋白水解靶向嵌合体 (PROTACs)，它劫持感兴趣的蛋白质 (POI) 并通过招募 E3 连接酶进行目标降解泛素-蛋白酶体通路是一种新的药物发现范式，已被广泛用作具有临床应用价值潜力的生物工具和药用分子。迄今为止，已经开发了多种小分子PROTAC。重要的是，基于 VHL 的 PROTAC 已成为一种很有前途的蛋白质方法，包括那些不可成药的蛋白质，例如转录因子和支架蛋白。基于 VHL 的 PRTOAC 已被开发用于治疗传统方法难以处理的疾病，例如放疗、化疗和小分子抑制剂。在这篇综述中，总结了基于 VHL 的 PRTOAC 的最新进展，并强调了与该领域相关的机遇和挑战。