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Triciribine, also known as API-2, NSC 154020, is a cell-permeable tricyclic nucleoside that inhibits the phosphorylation, activation, and signalling of Akt-1, -2, and -3. Akt-1, -2, and -3 are serine/threonine protein kinases in the phosphatidylinositol 3 (PI3)-kinase signalling pathway that play a critical role in the regulation of cell proliferation and survival. Triciribine induced autophagy, which could be interpreted as a defensive mechanism, because an autophagy inhibitor (chloroquine) increased triciribine-induced apoptosis. In vitro, Triciribine (API-2) significantly inhibits Akt-overexpressing human cancer cell lines growth with 50% inhibition at ~5-10 µM. It also inhibits DNA synthesis and displays antiviral activity against HIV-1 and -2. Combinations of triciribine with classic inhibitors targeting other molecules of the PI3K-AKT-pathway led to synergistic anti-proliferative effects.
| Cell Experiment | |
|---|---|
| Cell lines | LNCaP, PC-3, OVCAR3, OVCA8, PANC1, MDA-MB-468, and WM35 cells line |
| Preparation method | Screening for Inhibition of Akt-Transformed Cell Growth. AKT2 transformed NIH3T3 cells or LXSN vector-transfected NIH3T3 control cells (4) were plated into 96-well tissue culture plate. After treatment with 5 μM NCI Diversity Set compound, cell growth was detected with CellTier 96 One Solution Cell Proliferation kit (Promega). Compounds that inhibit growth in AKT2-transformed but not LXSN-transfected NIH3T3 cells were considered as candidates of Akt inhibitor and subjected to additional analysis. |
| Concentrations | 0~20 μM |
| Incubation time | 24 and 48 h |
| Animal Experiment | |
|---|---|
| Animal models | Nude Mouse Tumor Xenograft Model |
| Formulation | 20% DMSO |
| Dosages | 1 mg/kg/day |
| Administration | i.p. |
| Molecular Weight | 320.3 |
| Formula | C13H16N6O4 |
| CAS Number | 35943-35-2 |
| Solubility (25°C) | DMSO 54 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Related Akt Products |
|---|
| AT7867
AT7867 is a potent and oral inhibitor of AKT and p70 S6 kinase with an IC50 of 17 nM. |
| GSK690693
GSK690693 is a potent Akt inhibitor (Akt1 IC50 = 2 nM, Akt2 IC50 = 13 nM, Akt3 IC50 = 9 nM) which also inhibited the phosphorylation of the downstream target GSK3b in cells. |
| Perifosine
Perifosine is an orally active Akt inhibitor, the antiproliferative properties of Perifosine with an IC50 of 0.6–8.9 µM. |
| MK-2206 2HCl
MK-2206 is a novel allosteric inhibitor of Akt with IC50 values of 8 nM, 12 nM and 65 nM for Akt1, Akt2 and Akt3, respectively. |
| Ipatasertib
Ipatasertib (GDC-0068, RG7440) is a potent and selective, ATP-competitive Akt inhibitor with IC50 values of 5 to 18 nM. |
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