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

ABSTRACT: 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 an important role in tumor immune escape through the regulation of multiple immune cells and has been regarded as an attractive target for cancer immunotherapy. Proteolysis Targeting Chimeras (PROTAC) technology has emerged as a new model for drug research and development for its advantageous mechanism. Herein, we reported the application of PROTAC technology in targeted degradation of IDO1, leading to the discovery of the first IDO1 PROTAC degrader 2c, which induced significant and persistent degradation of IDO1 with maximum degradation (d _max) of 93% in HeLa cells. Western

SUBMITTER: Hu M 

PROVIDER: S-EPMC7606109 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature