Triciribine, 曲西立滨

Protein kinase B inhibitor;

Cell-permeable tricyclic nucleoside that inhibits the phosphorylation, activation and signalling of Akt. Selective over PKC, PKA, SGK and p38 pathways. Induces cell growth arrest and apoptosis in vitro.

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. Following recruitment of Akt to the plasma membrane, phosphorylation at threonine 308 and serine 473 (Akt-1 numbering) by phosphoinositide-dependent kinases (PDK) 1 and 2 results in full activation of the enzyme. Triciribine is a cell-permeable tricyclic nucleoside that inhibits the phosphorylation, activation, and signalling of Akt-1, -2, and -3.3 It does not inhibit phosphatidylinositol 3 (PI3)-Kinase or PDK1, the direct upstream activators of Akt, nor does it inhibit PKC, PKA, ERK1/2, serum- and glucocorticoid-inducible kinase, p38, STAT3, or JNK signalling pathways. Triciribine effectively inhibits growth of Akt-overexpressing human cancer cell lines in vitro with 50% inhibition at ~5-10 µM. It also inhibits the growth of tumor xenografts in mice by greater than 80% at a dose of 1 mg/kg/day.

Triciribine is an antitumor tricyclic nucleoside. Triciribine acts as a potent, small-molecule inhibitor of AKT phosphorylation in subjects with solid tumors contining activated AKT. Triciribine is also a selective inhibitor of HIV-1 and HIV-2, including strains known to be resistant to AZT or TIBO.

Triciribine, also known as VQD-002, is a potent AKT inhibitor and a cell-permeable tricyclic nucleoside molecule with potential antineoplastic activity. Triciribine inhibits the phosphorylation, activation, and signalling of Akt-1, -2, and -3, which may result in the inhibition of Akt-expressing tumor cell proliferation. Akts are anti-apoptotic serine/theronine-specific protein kinases that phosphorylate and inactivate components of the apoptotic machinery, including Bcl-xL/Bcl-2-associated death promoter (BAD) and caspase 9.