protac ido1 degrader 1

PROTAC IDO1 Degrader-1 is the first potent IDO1 (indoleamine 2,3-dioxygenase 1) degrader that hijacks IDO1 to CRBN E3 ligase to introduce IDO1 into UPS and eventually achieve ubiquitination and degradation (DC50=2.84 μM). PROTAC IDO1 Degrader-1 moderately improves the tumor-killing activity of H ER2 CAR-T cells[1]. PROTAC IDO1 Degrader-1 (compound 2c) (10 μM; 24 hours) notably decreases IDO1 level induced by IFN-γ[1].PROTAC IDO1 Degrader-1 and IFN-γ (5 ng mL) are incubated with HeLa cells for 24 h, and a significant dose-dependent degradation is observed. PROTAC IDO1 Degrader-1 combined with chimeric antigen receptor-modified T (CAR-T) cells can improve the tumor-killing activity of HER-2 CAR-T cells[1].PROTAC IDO1 Degrader-1 induces significant and persistent degradation of IDO1 with maximum degradation (dmax) of 93% in HeLa cells[1]. [1]. Hu M, et al. Discovery of the first potent proteolysis targeting chimera (PROTAC) degrader of indoleamine 2,3-dioxygenase 1. Acta Pharm Sin B. 2020;10(10):1943-1953.

NU227326 是一种吲哚胺 2,3-双加氧酶 1 (IDO1) 的PROTAC降解剂，具备 DC50为 4.5 nM 的活性。在细胞系U87和GBM43中，NU227326 对 IDO1 的降解作用分别为 DC50 7.1 nM 和 11.8 nM。此化合物还展现出优异的药代动力学性质，血浆半衰期为 5.7 小时，脑组织半衰期为 11.8 小时。(Pink: ligand for target protein IDO1 ligand-1; Black: linker; Blue: ligand for E3 ligase Cereblon)