Discovery of the first potent proteolysis targeting chimera (PROTAC) degrader of indoleamine 2,3-dioxygenase 1

• DOI: 10.1016/j.apsb.2020.02.010
• Publication Date: 2020-02-27T16:43:38Z
• Authors: Mingxing Hu; Weilin Zhou; Yijie Wang; Dongping Yao; Tinghong Ye; Yuqin Yao; Bin Chen; Gongping Liu; Xifei Yang; Wei Wang; Yongmei Xie
• Keywords: Indoleamine 2,3-dioxygenase; Protein Degradation; Proteolysis; Cancer Immunotherapy

Cancer immunotherapy is revolutionizing oncology and has emerged as a promising strategy for the treatment of multiple cancers. Indoleamine 2,3-dioxygenase 1 (IDO1), an immune checkpoint, plays important role in tumor escape through regulation cells been regarded attractive target cancer immunotherapy. Proteolysis Targeting Chimeras (PROTAC) technology new model drug research development its advantageous mechanism. Herein, we reported application PROTAC targeted degradation IDO1, leading to discovery first IDO1 degrader 2c, which induced significant persistent with maximum (dmax) 93% HeLa cells. Western-blot based mechanistic studies indicated that was degraded by 2c ubiquitin proteasome system (UPS). Label-free real-time cell analysis (RTCA) moderately improved tumor-killing activity chimeric antigen receptor-modified T (CAR-T) Collectively, these data provide insight immune-related proteins tool study function IDO1.