Home > Compound List > Product Information
Click picture or here to close


Catalog No. S1117 Name Selleck Chemicals
CAS Number 35943-35-2 Website http://www.selleckchem.com
M. F. C13H16N6O4 Telephone (877) 796-6397
M. W. 320.30394 Fax (832) 582-8590
Purity Email sales@selleckchem.com
Storage -20°C Chembase ID: 73145


IUPAC name
IUPAC Traditional name


CAS Number 35943-35-2


Target Akt
Salt Data Free base
Storage Condition -20°C


Description (English)
Biological Activity
Description Triciribine (TCN, API-2) is a DNA synthesis inhibitor and also inhibits Akt and HIV-1 with IC50 of 130 nM and 20 nM, respectively.
Targets Akt HIV-1
IC50 130 nM [1] 20 nM [2]
In Vitro Triciribine exhibits maximum growth inhibition around 1-10 μM and inhibits phosphorylation of Akt, as well as downstream p70S6K, to basal levels at 100μM (IC50 = 130 nM). Triciribine shows particular promise for inhibiting growth in Nf1 and Trp53 mutant astrocytoma cells in a grade-dependent manner. The WHO II K1861-10 line is inhibited, incompletely (69% maximum inhibition), with a GI50 value of 1.7 μM for Triciribine, whereas higher-grade tumor lines (KR158, KR130, and SF295) are inhibited to a greater extent (>80% maximum inhibition) at lower GI50 values (0.4–1.1 mM). Importantly, Triciribine is much less effective at inhibiting primary astrocytes (GI5013.6 mM), suggesting that this inhibitor may show specificity for tumor cells. [1] Triciribine inihibits HIV-1with an IC50 of 20 nM. Greater than 90% inhibition is achieved at 0.1μM and complete inhibition of syncytia formation is achieved at 5μM. Associated cell toxicity in the same cell line for Triciribine is 46 μM, resulting in selectivity indices of 2250. Triciribine markedly inhibits HIV-1-induced p24 core antigen production, reverse transcriptase, and infectious virus production in a dose-dependent manner using HIV-1 acutedly infected CEM-SS, H9, and persistently infected H9III B and U1 cells. [2] Triciribine inhibits Akt phosphorylation at Thr308 and Ser473 and Akt activity in the human prostate cancer cell line PC-3. Triciribine sensitizes PC-3 cells to TRAIL- and anti-CD95-induced apoptosis, whereas the cells remain resistant to DNA damaging chemotherapeutics. [3] Triciribine is highly selective for Akt and does not inhibit the activation of phosphatidylinositol 3_-kinase, phosphoinositide-dependent kinase-1, protein kinase C, serum and glucocorticoid-inducible kinase, protein kinase A, signal transducer and activators of transcription 3, extracellular signal-regulated kinase-1/2, or c-Jun NH2-terminal kinase. [4]
In Vivo 1 mg/kg/day i.p. treated Triciribine inhibits OVCAR3, OVCAR8 and PANC1 tumor growth, which overexpressing Akt, by 90%, 88% and 80% in nude mice, respectively. However, Triciribine has little effect on the growth of OVCAR5 and COLO357 cells. [4]
Clinical Trials Triciribine is now under the Phase I clinical trial for the safety study of human anti-cytomegalovirus monoclonal antibody.
Combination Therapy
Description Triciribine potentiates growth inhibition by trastuzumab over a 20-fold concentration range. Under combined therapy, breast cancer cell growth is inhibited and apoptosis is induced. Many of the tumors actually decreases in size and four of seven mice have no palpable tumors after 5 weeks of treatment. [5]
Kinase Assay [1]
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).
Assays for reverse transcriptase activity and p24 core antigen production Virus particles are precipitated from cell-free supernatant as follows: 0.3 mL of 4 M NaCl and 3.6 ml of 30% (wt/vol) polyethylene glycol are added to 7.5 mL of particle-containing medium and the suspension is placed on ice for 2 hours. The suspension is centrifuged in a Sorvall RC-3 centrifuge at 2100 rpm at 4 °C for 45 minutes. The precipitate is resuspended in 200 μL of 50% (vol/vol) glycerol/25 mM Tris-HCl, pH 7.5/5 mM dithiothreitol/ 50 mM KCI/0.025% Triton X-100. Virus particles are disrupted by addition of 100 μL of 0.9% Triton X-100/1.5 M KCI (solution 2). DNA polymerase assays are performed at 37 °C for 1 hour with a 10-μL aliquot of the disrupted virus solution in a final volume of 100 μL containing 40 mM Tris-HC1 (pH 7.8), 4 mM dithiothreitol, 45 mM KCl, and 50 μg of template-primer poly(A)-dT12-18 and poly(C).dG12-18 per mL (with 10 mM Mg2+) or 50 μg of poly(dA).dT12-18 per mL (with 0.25 mM Mn2+). The mixture also contains 15 μM of the appropriate labeled deoxyribonucleoside triphosphates, [3H] dTTP (16 Ci/mmol; 1 Ci = 3.7 × 1010 becquerels) or [3 H]dGTP (12 Ci/mmol). The peak activities are also assayed with various Mg2+ and Mn2+ concentrations with each template-primer, and this activity is compared with that of SSV(simian sarcoma virus-associated virus) [SSV(SSAV)] RT and human DNA polymerases α and γ. For assay of p24 core antigen, the HIV-1 antigen MicroELISA system is used.
Cell Assay [2]
Cell Lines CEM-SS cells
Concentrations 0-500 μM
Incubation Time 48 hours
Methods 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.
Animal Study [4]
Animal Models OVCAR3, OVCAR8, PANC1, OVCAR5 and COLO357 tumor cells are injected s.c. into 80week-old female nude mice.
Formulation Triciribine is dissolved in 20% DMSO.
Doses 1 mg/kg/day
Administration Triciribine is administrated through i.p. injection once a day.
[1] Gursel DB, et al, Nero Oncol, 2011, 13(6), 610-621.
[2] Kucera LS, et al, AIDS Res Hum Retroviruses, 1993, 9(4), 307-314.
[3] Dieterle A, et al, Int J Cancer , 2009, 125(4), 932-941.
[4] Yang L, et al, Cancer Res, 2004, 64(13), 4394-4399.
[5] Lu CH, et al, Clin Cancer Res, 2007, 13(19), 5883-5888.