TDO-IN-1

TDO-IN-1 is an orally active and selective inhibitor of tryptophan 2,3-dioxygenase (TDO), shows excellent selectivity over indoleamine-2,3-dioxygenase (IDO), with an IC50 value of 0.62 μM (IDO). TDO-IN-1 reverse the local immune tolerance of tumor tissue to inhibit tumor growth in vivo[1].

Research Areas >> Cancer

Signaling Pathways >> Others >> Others

IC50: 0.62 μM (tryptophan 2,3-dioxygenase, TDO)[1]

TDO-IN-1 (HT-28) (0-100 μM; 24 h) shows significant tumoricidal effect on different tumor lines, with IC50s of 0.54 μM (HepG2), 5.08 μM (Hepa1-6), 1.34 μM (H22), 37.39 μM (B16), 3.43 μM (MOLM-13), and 7.25 μM (Jurkat), respectively[1]. TDO-IN-1 (0-100 μM; 24 h) exhibits few cytotoxic activity against normal cells (HEK 293 cells) below 10 μM[1].

TDO-IN-1 (HT-28) (25 mg/kg; p.o.; once daily; 9 d) improve the effect of tumor immunotherapy of CT26 tumor expressing TDO, substantially inhibits the proliferation of CT26 tumors in mice[1]. Animal Model: CT-26 allograft BALB/c mice (6-8 weeks old, female)[1] Dosage: 12.5, 25, and 50 mg/kg Administration: Oral gavage; once daily; 9 days Result: Resulted significant reduction in tumor weight and volume in mice, with the tumor volume inhibiton rate of 76.93%. Reduced the expression of Foxp3 and enhance the expression of CD8 and TNF-α in tumor tissue to increase the immune response of tumor-bearing mice.

[1]. Huo C, et al. 4,6-Disubstituted-1H-Indazole-4-Amine derivatives with immune-chemotherapy effect and in vivo antitumor activity. Eur J Med Chem. 2022 Nov 5;241:114625.