Background:

Triciribine is an inhibitor of DNA synthesis for Akt and HIV-1 with IC50 values of 130 nM and 20 nM, respectively. [1,2]
Protein kinase B (PKB), also known as Akt, is a serine/threonine-specific protein kinase that plays a key role in multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription and cell migration. Once PH domain of Akt bind phospholipids ,the activated Akt can then go on to activate or deactivate its myriad substrates via its kinase activity. e.g. Nuclear Factor-kB, Bcl-2 family proteins and murine double minute 2 (MDM2).[3] Studies show that tumor cells have constantly active Akt depending on Akt for survival [4], so Akt inhibitors may treat cancers.
Triciribine, also known as API-2, suppresses the phosphorylation level and kinase activity of Akt, result in induce apoptosis and cell growth in cancer cell. Triciribine can specifically inhibit the most common astrocytic tumor cells inhibitory efficiency was very low (13.6 mM [5] GI50). Triciribine can inhibit HIV-1, IC50 20 nM. The amount of inhibition of 0.1 M can produce >90% ratio, dosage of 5 M could completely inhibit coenocytic. In the same cell line cytotoxicity test results showed when the concentration of Triciribine for the selective index of 46 M to 2250 using HIV-1 infected CEM-SS, H9, and B and U1 persistent infection of H9III cells of p24 core antigen, Triciribine can significantly inhibit HIV-1 induced generation, reverse transcriptase and the generation of infectious virus, this inhibition is dose dependent characteristics [6]. Triciribine inhibits human prostate cancer cell line PC-3 in the Akt 308 bit acid and serine 473 phosphorylation and Akt activity. Triciribine make PC-3 cells more sensitive to apoptosis induced by TRAIL- and anti-CD95, but to DNA damage caused by chemotherapy is still resistance [7]. Triciribine also can selectively inhibit Akt1, Akt2, and Akt3 without inhibiting known upstream activators, PDK1 and PI3K, of Akt. Additionally, Triciribine has antineoplastic and antiviral activity at low micromolar and submicromolar concentrations, and has been demonstrated to inhibit incorporation of amino acids into proteins and purine nucleotide synthesis.
Reference:
1 Gursel DB, et al. “Control of proliferation in astrocytoma cells by the receptor tyrosine kinase/PI3K/AKT signaling axis and the use of PI-103 and TCN as potential anti-astrocytoma therapies”. Nero Oncol, 2011, 13(6), 610-621.
2 Kucera LS, et al, AIDS Res Hum Retroviruses, 1993, 9(4), 307-314.
3 Song G, Ouyang G, Bao S. "The activation of Akt/PKB signaling pathway and cell survival". J. Cell. Mol. Med, 2005, 9 (1): 59-71.
4 Lindhurst MJ, Sapp JC, Teer JK, Johnston JJ, Finn EM, Peters K et al. "A mosaic activating mutation in AKT1 associated with the Proteus syndrome". N. Engl. J. Med, 2011, 365 (7): 611-9.
5 Gursel DB, et al, Nero Oncol, 2011, 13(6), 610-621.
6 Dieterle A, et al, Int J Cancer , 2009, 125(4), 932-941.
7 Yang L, et al, Cancer Res, 2004, 64(13), 4394-4399.