TCS-PIM-1-4a (SMI-4a) is a pan-Pim kinases inhibitor that blocks mTORC1 activity via activation of AMPK. TCS-PIM-1-4a kills a wide range of both myeloid and lymphoid cell lines (IC50 values ranging from 0.8 μM to 40 μM).
IC50&Target
Pim
体外研究
TCS-PIM-1-4a (10 μM; 24-48 hours; 6812/2 cells and Jurkat cells) treatment increases the population of cells in the G1 phase from 44.3% to 68.4% and from 56.2% to 67.1% in 6812/2 and Jurkat, respectively. S-phase cells are decreased in 6812/2, whereas only small changes are seen in Jurkat cells consistent with the lesser G1 block.
TCS-PIM-1-4a (5 μM; 6 hours; 6812/2 cells and Jurkat cells) induces cell death by the induction of apoptosis.
TCS-PIM-1-4a (5 μM; 4-8 hours; 6812/2 cells and Jurkat cells) prevents the increase in 4E-BP1 protein levels and inhibits mTOR-directed phosphorylation on Thr37/46.
Cell Cycle Analysis
Cell Line:
6812/2 cells and Jurkat cells
Concentration:
10 μM
Incubation Time:
24 hours, 48 hours
Result:
Induced cell-cycle arrest.
Apoptosis Analysis
Cell Line:
6812/2 cells and Jurkat cells
Concentration:
5 μM
Incubation Time:
6 hours
Result:
Led to an increase in the number of the cells positive for annexin V and negative for PI from 8.25% in the control to 21.85%.
Western Blot Analysis
Cell Line:
6812/2 cells and Jurkat cells
Concentration:
10 μM
Incubation Time:
4 hours, 8 hours
Result:
Prevented the increase in 4E-BP1 protein levels and inhibited mTOR-directed phosphorylation on Thr37/46.
体内研究
TCS-PIM-1-4a (SMI-4a; 60 mg/kg; oral gavage; twice daily; for 21 days; nu/nu nude mice) treatment causes a significant delay in the tumor growth without any change in the weight, blood counts, or chemistries.
Animal Model:
18 Nu/nu nude mice with 6812/2 murine pre–T-LBL cells
Dosage:
60 mg/kg
Administration:
Oral gavage; twice daily; for 21 days
Result:
Caused a significant delay in the tumor growth.
分子式
C11H6NO2F3S
分子量
273.23
CAS号
327033-36-3
运输条件
Room temperature in continental US; may vary elsewhere.