State Key Laboratory of Biotherapy and Cancer Center, Innovation Center of Nursing Research, Nursing Key Laboratory of Sichuan Province, National Clinical Research Center for Geriatrics, West China Hospital, and Collaborative Innovation Center of Biotherapy, Sichuan University, Chengdu 610041, China.
Chem Commun (Camb). 2021 Dec 7;57(97):13194-13197. doi: 10.1039/d1cc04661f.
Autophagy-based protein degradation is emerging as a promising technology for anti-diseases and innovative drug discovery. Here, we demonstrate a novel type of autophagy-targeting chimera (AUTAC) to degrade protein by targeting autophagy key protein LC3. The best compound 10f powerfully degraded BRD4 protein through the autophagy pathway and exhibited good anti-proliferative activity in multiple tumor cells, providing a powerful toolbox for medicinal chemists to study disease-related targets with autophagy-based degradation.
基于自噬的蛋白质降解技术正在成为一种有前途的抗疾病和创新药物发现的技术。在这里，我们展示了一种新型的自噬靶向嵌合体（AUTAC），通过靶向自噬关键蛋白 LC3 来降解蛋白质。最佳化合物 10f 通过自噬途径强力降解 BRD4 蛋白，并在多种肿瘤细胞中表现出良好的抗增殖活性，为药物化学家提供了一个强大的工具箱，用于研究与自噬降解相关的疾病相关靶标。
