Triciribine

SKU: orb1301105

Description

Triciribine (NSC-154020) is a small molecule inhibitor of Akt and HIV-1/2, and it also suppresses DNA synthesis. It is used in cancer research, particularly for studying PI3K/Akt signaling pathways, and has been investigated in both in vitro and in vivo experimental models.

Research Area

Cell Biology, Infectious Disease & Virology, Molecular Biology, Protein Biochemistry, Signal Transduction

Key Properties

• CAS Number: 35943-35-2
• MW: 320.3
• Purity: >99.99% (May vary between batches)
• Formula: C₁₃H₁₆N₆O₄
• SMILES: Cn1nc(N)c2cn([C@@H]3C[C@H](CO)[C@@H](O)[C@H]3O)c3ncnc1c23
• Target: DNA/RNA Synthesis,Akt,HIV Protease
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (6.24 mM);DMSO:106 mg/mL (330.94 mM)

Bioactivity

• Target IC50:
  Akt:130 nM|HIV-2:0.02-0.46 μM|HIV-1:20 nM
• 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.
• 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 100 μM (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. Triciribine inihibits HIV-1with an IC50 of 20 nM. Greater than 90% inhibition is achieved at 0.1 μM and complete inhibition of syncytia formation is achieved at 5 μM. 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. 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. 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.
• Cell Research:
  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)

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Human immunodeficiency virus, HIV, HIVProtease, HIV-1, HIV Protease, Inhibitor, NSC 154020, NSC154020, NSC-154020, inhibit, DNA/RNA Synthesis, DNA Synthesis, DNASynthesis, API 2, API2, API-2, Akt, Protein kinase B, PKB, TCN, Tricyclic nucleoside, Triciribine, RNA Synthesis, RNASynthesis, VD0002, VD-0002, VD 0002

Compound Identifiers

PubChem CID

118704601