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.
ML-T7 是一种有效的 Tim-3 抑制剂,阻断 Tim-3 与 PtdSer 和 CEACAM1 的相互作用,增强 CTLs 和 CAR T 细胞过继转移治疗的抗肿瘤活性及 T 细胞的效应功能,促进 NK 细胞对肿瘤细胞的杀伤活性和 DC 抗原呈递能力;单独使用或与 Nivolumab 联合使用可在临床前肿瘤模型中发挥抗肿瘤功效。ML-T7 可用于肿瘤免疫治疗研究。