化合物 T29018
化合物 T29018 用途与合成方法
EC50: 2.8 nM (TrxR)
TrxR inhibitor D9 (0.1-1 μM; 72 h) inhibits the cell proliferation with IC
50
s of 0.03 and 0.1 μM for MCF-7 and HT-29 cells, respectively.
TrxR inhibitor D9 (72 h) completely inhibits all cancer cells (A549, KB, MDA MB-231, HeLa, MCF-7 and HT-29) viability at the concentration of 0.60 μM, and the IC
50
s of all cancer cells could be as low as 0.55 μM, and dose not significantly affects normal cells viability.
TrxR inhibitor D9 (0.8 μM; 4 and 8 h) induces HT-29 cells necrosis/apoptosis.
TrxR inhibitor D9 (2-20 nM; 1-60 s) inhibits TrxR activity in a concentration-dependent manner.
TrxR inhibitor D9 (1-1000 nM) does not significantly inhibits the catalytic activity of glutathione reductase (GR) even when the concentration increases to more than 1000 nM.
TrxR inhibitor D9 (0.4 μM) could effectively avoid the ligand exchange with albumin.
Cell Proliferation Assay
| Cell Line: | MCF-7 and HT-29 cells |
| Concentration: | 0.1, 0.5, 1 μM |
| Incubation Time: | 72 hours |
| Result: | Killed 70% MCF-7 cells and 50% HT-29 cells with the concentration as low as 0.1 μM. |
Apoptosis Analysis
| Cell Line: | MCF-7 cells |
| Concentration: | 0.8 μM |
| Incubation Time: | 4 and 8 hours |
| Result: |
Led to more than 50% necrosis/apoptosis of cells compared to control after 4 h of treatment.
Induced all cells necrosis/apoptosis after 8 h of incubation. |
TrxR inhibitor D9 (5 mg/kg; i.v. once every 2 d for 15 d) effectively inhibits the growth of tumors in mice.
| Animal Model: | BALB/c nude mice (17-18 g) bearing a MCF-7 tumor |
| Dosage: | 5 mg/kg |
| Administration: | I.v. once every 2 days for 15 days |
| Result: | Inhibited tumor growth with IR (inhibition ratio) of 91.5% and was well tolerated. |
