Triciribine (NSC-154020) is a DNA synthesis inhibitor, and it also inhibits Akt and HIV-1/2.

HIV-1:20 nM, Akt:130 nM

Triciribine 在1-10 μM 范围内展现出最大的生长抑制作用，且在100 μM 时能够将Akt及其下游的p70S6K的磷酸化水平抑制至基础水平（IC50 = 130 nM）。特别地，Triciribine 对于Nf1和Trp53突变的星形细胞瘤细胞的生长抑制表现出等级依赖性的承诺。WHO II K1861-10 线被部分抑制（最大抑制率为69%），Triciribine 的GI50值为1.7 μM，而更高级别的肿瘤线（KR158, KR130, 和 SF295）在更低的GI50值（0.4–1.1 mM）下被更大程度地抑制（>80%最大抑制率）。重要的是，Triciribine 对初级星形胶质细胞的抑制作用较弱（GI50 13.6 mM），这表明这种抑制剂可能对肿瘤细胞具有特异性。[1] Triciribine 对HIV-1的IC50为20 nM，在0.1 μM 时可实现超过90%的抑制，而在5 μM 时能完全抑制合胞体形成。Triciribine 在同一细胞系中的相关细胞毒性为46 μM，从而得到2250的选择性指数。Triciribine 显著地以剂量依赖性方式抑制HIV-1急性感染的CEM-SS、H9细胞和持续感染的H9III B和U1细胞中的p24核心抗原生产、逆转录酶和传染性病毒生产。[2] Triciribine 抑制人前列腺癌细胞系PC-3中的Akt在Thr308和Ser473的磷酸化和Akt活性，使PC-3细胞对TRAIL和抗CD95诱导的凋亡敏感，而对DNA损伤化疗药物则保持抵抗。[3] Triciribine 对Akt具有高度选择性，不抑制磷脂酰肌醇3激酶、磷脂酰肌醇依赖性激酶-1、蛋白激酶C、血清和糖皮质激素诱导激酶、蛋白激酶A、信号转导和转录激活因子3、外胞素信号调节激酶-1/2或c-Jun NH2-末端激酶的激活。[4]

1 mg/kg/日经腹膜注射的Triciribine对过度表达Akt的OVCAR3、OVCAR8和PANC1肿瘤生长在裸鼠中分别抑制了90%、88%和80%。然而，Triciribine对OVCAR5和COLO357细胞的生长影响甚微。[4]

Akt Phosphorylation Changes Assay: Cells are grown to 80%–90% confluency and stimulated for 5–10 minutes with 1–10 ng/mL of epidermal growth factor or platelet derived growth factor (PDGF)–AA with or without 10–20 mM of U0126 or LY-294002. Protein lysates (5–20 μg) are separated by 12%–15% SDS PAGE and analyzed by Western blot for Akt, phosphorylated Akt (phospho-Ser 473), MAPK, and phosphorylated MAPK (p44/42 phospho-Thr202/Tyr204) antibodies (1:1000).

Triciribine is evaluated for cytotoxicity by seeding CEM-SS cells at a density of 1 × 104 cells/well in growth medium, using a 96-well flat-bottom plate. Serial fivefold dilutions of Triciribine are prepared in growth medium and added to the wells as a second overlay. After a 48-hours incubation at 37 °C, the cells are pulse labeled with [3H]dThd (1 μCi per well, specific activity 20 Ci/mmol) for 6 hours and the cells are harvested to measure total DNA synthesis.(Only for Reference)