| Triciribine is a potent Akt inhibitor with IC50 of 130 nM. Triciribine also potently and selectively inhibits HIV-1 with an IC50 of 20 nM. Triciribine significantly inhibits Akt 2 phosphorylation at both threonine 309 and serine 474, which are required for full activation of Akt 2. Triciribine also suppresses EGF-induced kinase activity and phosphorylation of Akt 1, Akt 2, and Akt 3. Triciribine inhibits phosphorylation levels of Akt only in the cells (OVCAR3, OVCAR8, PANC1, and Akt 2-transformed NIH3T3) expressing elevated Akt or responding to insulin-like growth factor-I simulation. Accordingly, triciribine inhibits cell growth to a much higher degree in Akt-overexpressing/activating cells compared with those with low levels of Akt. Triciribine treatment (20 µM) inhibits cell proliferation by approximately 50-60% in Akt-overexpressing/activating cell lines, LNCaP, PC-3, OVCAR3, OVCA8, PANC1, MDA-MB-468, and WM35, whereas only by about 10-20% in DU145, OVCAR5, COLO357, T47D, and WM852 cells, which exhibit low levels of Akt or do not respond to growth stimulation by insulin-like growth factor-I. Moreover, triciribine induces apoptosis by 8-fold (OVCAR3), 6-fold (OVCAR8), 6-fold (PANC1), and 3-fold (AKT2-NIH3T3) compared to vehicle (DMSO) treatment. Triciribine (1 µM) treatment partially attenuates the phosphorylation levels of Bad, GSK-3β, and AFX in OVCAR3 cells.[1] Triciribine at 0.1 µM achieves >90% inhibition of syncytia formation and triciribine at 5 µM achieves complete inhibition of syncytia formation in acutely HIV-1 infected CEM-SS cells. Furthermore, triciribine has potent antiviral activity against both HIV-1 and HIV-2 isolates. In human peripheral blood leukocytes (PBLs) acutely infected with HIV-1, triciribine inhibits infectious virus production and HIV-1 -induced reverse transcriptase in a dose-dependent manner, but not p24 core antigen. In other acutely infected cells (H9T cells), IC50 values of triciribine for infectious virus, reverse transcriptase, and p24 core antigen range from 0.01 to 0.03 µM.[2] In tumor models that overexpress Akt, triciribine (1 mg/kg/day) inhibits OVCAR3, OVCAR8, and PANC1 tumor growth by 90, 88, and 80%, respectively. In treated tumor samples, Akt activity is inhibited by triciribine without a change of total Akt content.[1] In BT474.m1 cell xenografts model, combination treatment with triciribine and trastuzumab dramatically and significantly inhibits tumor growth. Besides, many of the tumors actually decrease in size and four of seven mice have no palpable tumors after 5 weeks of combination treatment with triciribine and trastuzumab.[3] |
