Triciribine (API-2)

Akt inhibitor

Home PI3K/Akt/mTOR Akt inhibitor - DNA/RNA Synthesis inhibitor - HIV inhibitor Triciribine (API-2)

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Triciribine (API-2) is a DNA synthesis inhibitor, also inhibits Akt in PC3 cell line and HIV-1 in CEM-SS, H9, H9IIIB, U1 cells with IC50 of 130 nM and 20 nM, respectively; does not inhibit PI3K/PDK1; 5000-fold less active in cells lacking adenosine kinase. Phase 1/2.

Triciribine (API-2) Chemical Structure

Triciribine (API-2) Chemical Structure

Molecular Weight: 320.3

Purity & Quality Control

Triciribine (API-2) Related Products

Signaling Pathway

Akt Signaling Pathways

Akt Signaling Pathway

Cell Culture and Working Concentration

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
L1210 Function assay Tested in vitro for cytotoxicity against murine L1210 leukemic cells, IC50=0.035μM 10882371
HFF Function assay HCMV plaque assay was performed using HFF cells and effect was calculated as a percentage of reduction in number of plaques, IC50=2.5μM 10882371
BSC-1 Antiviral assay Antiviral activity was tested using an enzyme-linked immunosorbent assay (ELISA) to detect HSV-1 (herpes simplex virus type 1) using BSC-1 cells, IC50=23μM 10882371
HFF Antiviral assay Antiviral activity against HCMV was determined by plaque reduction assay using HFF cells, IC50=2.5μM 10882373
AA2 Function assay 5 hrs Intracellular phosphorylation (100 uM) in uninfected AA2 cells was studied after 5 hrs of Incubation., Concentration=9μM 10882373
BSC-1 Antiviral assay Antiviral activity against HSV-1 was determined using BSC-1 cells by an enzyme-linked immunosorbent assay (ELISA), IC50=23μM 10882373
Huh-7 Function assay Compound was tested for its ability to inhibit hepatitis C viral RNA replication in Huh-7 cells (human hepatoma cells), EC50=2μM 15177464
MCF7 Cytotoxicity assay Cytotoxicity against human MCF7 cells in presence of 20 uM chloroquine by SRB assay, GI50=0.05μM 18691894
MCF7 Cytotoxicity assay Cytotoxicity against human MCF7 cells in presence of 10 uM chloroquine by SRB assay, GI50=0.56μM 18691894
MDA-MB-231 Cytotoxicity assay Cytotoxicity against human MDA-MB-231 cells in presence of 20 uM chloroquine by SRB assay, GI50=0.69μM 18691894
MCF7 Cytotoxicity assay Cytotoxicity against human MCF7 cells by SRB assay, GI50=3.64μM 18691894
MDA-MB-468 Cytotoxicity assay Cytotoxicity against human MDA-MB-468 cells in presence of 20 uM chloroquine by SRB assay, GI50=10.29μM 18691894
184B5 Cytotoxicity assay 20 uM Cytotoxicity against human 184B5 cells at 20 uM chloroquine by SRB assay, GI50=16.96μM 18691894
MDA-MB-468 Cytotoxicity assay 10 uM Cytotoxicity against human MDA-MB-468 cells in presence of 10 uM chloroquine by SRB assay, GI50=20.45μM 18691894
184B5 Cytotoxicity assay 10 uM Cytotoxicity against human 184B5 cells at 10 uM chloroquine by SRB assay, GI50=34μM 18691894
MDA-MB-231 Cytotoxicity assay 10 uM Cytotoxicity against human MDA-MB-231 cells in presence of 10 uM chloroquine by SRB assay, GI50=37μM 18691894
184B5 Cytotoxicity assay Cytotoxicity against human 184B5 cells by SRB assay, GI50=40μM 18691894
MDA-MB-468 Cytotoxicity assay Cytotoxicity against human MDA-MB-468 cells by SRB assay, GI50=43.53μM 18691894
MDM Antiviral assay 6 days Antiviral activity against Human immunodeficiency virus 1 ADA infected in human MDM cells assessed as expression of p24 antigen after 6 days postinfection by ELISA, IC50=0.006μM 20086149
ACH2 Cytotoxicity assay Cytotoxicity against human ACH2 cells infected with latent Human immunodeficiency virus 1 by MTS assay, CC50=0.01μM 20086149
ACH2 Cytotoxicity assay Cytotoxicity against human ACH2 cells infected with latent Human immunodeficiency virus 1 by MTS assay in presence of tumor necrosis factor alpha, CC50=0.01μM 20086149
CEM-SS Antiviral assay 6 days Antiviral activity against Human immunodeficiency virus 1 3B infected in human CEM-SS cells infected with 0.78 uL of virus stock assessed as expression of p24 antigen after 6 days postinfection by ELISA, IC50<0.01μM 20086149
MDM Antiviral assay 6 days Antiviral activity against Human immunodeficiency virus 1 BAL infected in human MDM cells assessed as expression of p24 antigen after 6 days postinfection by ELISA, IC50=0.018μM 20086149
H9 Antiviral assay Antiviral activity against Human immunodeficiency virus 1 SK1 infected in human H9 cells assessed as inhibition of viral Reverse transcriptase by [3H]TTP incorporation assay, IC50=0.036μM 20086149
CEM-SS Antiviral assay Antiviral activity against Human immunodeficiency virus 1 3B expressing nef protein infecting in CEM-SS cells assessed as inhibition of viral Reverse transcriptase by [3H]TTP incorporation assay, IC50=0.04μM 20086149
CEM-SS Antiviral assay Antiviral activity against Human immunodeficiency virus 1 3B infected in human CEM-SS cells infected with 0.78 uL of virus stock assessed as inhibition of viral Reverse transcriptase by [3H]TTP incorporation assay, IC50=0.08μM 20086149
H9 Antiviral assay Antiviral activity against Human immunodeficiency virus 1 3B infected in human H9 cells infected with 25 uL of virus stock assessed as inhibition of viral Reverse transcriptase by [3H]TTP incorporation assay, IC50<0.1μM 20086149
H9 Antiviral assay Antiviral activity against Human immunodeficiency virus 1 3B infected in human H9 cells infected with 12.5 uL of virus stock assessed as inhibition of viral Reverse transcriptase by [3H]TTP incorporation assay, IC50<0.1μM 20086149
H9 Antiviral assay Antiviral activity against Human immunodeficiency virus 1 3B infected in human H9 cells infected with 6.25 uL of virus stock assessed as inhibition of viral Reverse transcriptase by [3H]TTP incorporation assay, IC50<0.1μM 20086149
H9 Antiviral assay 6 days Antiviral activity against Human immunodeficiency virus 1 3B infected in human H9 cells infected with 12.5 uL of virus stock assessed as expression of p24 antigen after 6 days postinfection by ELISA, IC50<0.1μM 20086149
H9 Antiviral assay 6 days Antiviral activity against Human immunodeficiency virus 1 3B infected in human H9 cells infected with 6.25 uL of virus stock assessed as expression of p24 antigen after 6 days postinfection by ELISA, IC50<0.1μM 20086149
CEM-SS Antiviral assay Antiviral activity against Human immunodeficiency virus 1 SK1 infected in human CEM-SS cells assessed as inhibition of viral Reverse transcriptase by [3H]TTP incorporation assay, IC50=0.13μM 20086149
ACH2 Antiviral assay 3 days Antiviral activity against 5 x 10'3 cells/well Human immunodeficiency virus 1 infected in human ACH2 cells assessed as inhibition of viral Reverse transcriptase after 3 days by [3H]TTP incorporation assay in presence of 5 ng/ml tumor necrosis factor alpha, IC50=0.15μM 20086149
AA5 Antiviral assay Antiviral activity against of Human immunodeficiency virus 1 3B infected in AA5 cells infected with 3.13 uL of virus stock assessed as inhibition of viral Reverse transcriptase by [3H]TTP incorporation assay, IC50<0.17μM 20086149
AA5 Antiviral assay Antiviral activity against of Human immunodeficiency virus 1 3B infected in AA5 cells infected with 1.56 uL of virus stock assessed as inhibition of viral Reverse transcriptase by [3H]TTP incorporation assay, IC50<0.17μM 20086149
AA5 Antiviral assay Antiviral activity against of Human immunodeficiency virus 1 3B infected in AA5 cells infected with 0.78 uL of virus stock assessed as inhibition of viral Reverse transcriptase by [3H]TTP incorporation assay, IC50<0.17μM 20086149
CEM-SS Antiviral assay 6 days Antiviral activity against Human immunodeficiency virus 1 3B infected in human CEM-SS cells infected with 1.56 uL of virus stock assessed as expression of p24 antigen after 6 days postinfection by ELISA, IC50=0.19μM 20086149
CEM-SS Antiviral assay Antiviral activity against Human immunodeficiency virus 1 harboring plasmid NL4-3 infected in CEM-SS cells assessed as inhibition of viral Reverse transcriptase by [3H]TTP incorporation assay, IC50=0.2μM 20086149
U1 Antiviral assay Antiviral activity against Human immunodeficiency virus 1 infected in human U1 cells assessed as inhibition of viral Reverse transcriptase by [3H]TTP incorporation assay, IC50=0.23μM 20086149
CEM-SS Antiviral assay 6 days Antiviral activity against Human immunodeficiency virus 1 3B infected in human CEM-SS cells infected with 3.13 uL of virus stock assessed as expression of p24 antigen after 6 days postinfection by ELISA, IC50=0.24μM 20086149
U1 Cytotoxicity assay Cytotoxicity against human U1 cells infected with latent Human immunodeficiency virus 1 by MTS assay, CC50=0.28μM 20086149
U1 Cytotoxicity assay Cytotoxicity against human U1 cells infected with latent Human immunodeficiency virus 1 by MTS assay in presence of tumor necrosis factor alpha, CC50=0.28μM 20086149
CEM-SS Antiviral assay Antiviral activity against Human immunodeficiency virus 1 3B infected in human CEM-SS cells infected with 1.56 uL of virus stock assessed as inhibition of viral Reverse transcriptase by [3H]TTP incorporation assay, IC50=0.29μM 20086149
CEM-SS Antiviral assay Antiviral activity against Human immunodeficiency virus 1 3B infected in human CEM-SS cells infected with 3.13 uL of virus stock assessed as inhibition of viral Reverse transcriptase by [3H]TTP incorporation assay, IC50=0.3μM 20086149
CEM-SS Antiviral assay Antiviral activity against Human immunodeficiency virus 1 D1 harboring Tyr127His mutation in nef protein infecting in CEM-SS cells assessed as inhibition of viral Reverse transcriptase by [3H]TTP incorporation assay, IC50=0.33μM 20086149
CEM-SS Antiviral assay Antiviral activity against Human immunodeficiency virus 1 A7 harboring Tyr127His mutation in nef protein infecting in CEM-SS cells assessed as inhibition of viral Reverse transcriptase by [3H]TTP incorporation assay, IC50=0.5μM 20086149
MDM Cytotoxicity assay Cytotoxicity against human MDM cells infected with Human immunodeficiency virus 1 BAL by MTS assay, TC50=0.66μM 20086149
CEM-SS Antiviral assay Antiviral activity against Human immunodeficiency virus 2 ROD infected in human CEM-SS cells assessed as inhibition of viral Reverse transcriptase by [3H]TTP incorporation assay, IC50=1.4μM 20086149
H9 Antiviral assay Antiviral activity against Human immunodeficiency virus 1 3B infected in human H9 cells infected with 50 uL of virus stock assessed as inhibition of viral Reverse transcriptase by [3H]TTP incorporation assay, IC50=1.53μM 20086149
H9 Cytotoxicity assay Cytotoxicity against human H9 cells by MTS assay, IC50=16.3μM 20086149
H9 Cytotoxicity assay Cytotoxicity against human H9 cells by MTS assay, CC50=19.6μM 20086149
Click to View More Cell Line Experimental Data

Mechanism of Action

Description Triciribine (API-2) is a DNA synthesis inhibitor, also inhibits Akt in PC3 cell line and HIV-1 in CEM-SS, H9, H9IIIB, U1 cells with IC50 of 130 nM and 20 nM, respectively; does not inhibit PI3K/PDK1; 5000-fold less active in cells lacking adenosine kinase. Phase 1/2.
Targets
HIV-1 [2]
(CEM-SS, H9, H9IIIB, U1 cells)		 Akt [1]
(PC3 cells)
20 nM 130 nM

In vitro
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]
Kinase Assay 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).
Cell Research Cell lines CEM-SS cells
Concentrations 0-500 μM
Incubation Time 48 hours
Method 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.
Experimental Result Images Methods Biomarkers Images PMID
Western blot PUMA / p-FoxO3a / p-AKT S1117-WB1 20978166
Immunofluorescence TRF2 / 53BP1 S1117-IF1 23862686

In Vivo
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]
Animal Research Animal Models OVCAR3, OVCAR8, PANC1, OVCAR5 and COLO357 tumor cells are injected s.c. into 80week-old female nude mice.
Dosages 1 mg/kg/day
Administration Triciribine is administrated through i.p. injection once a day.
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02987127 Unknown status
Mucosa-Associated Lymphoid Tissue Lymphoma
National Taiwan University Hospital
 February 2016 --
NCT00642031 Completed
Hematologic Malignancies|Leukemia
Prescient Therapeutics Ltd.|VioQuest Pharmaceuticals
 August 2006 Phase 1

References
  • https://pubmed.ncbi.nlm.nih.gov/21636709/
  • https://pubmed.ncbi.nlm.nih.gov/7685612/
  • https://pubmed.ncbi.nlm.nih.gov/19422047/
  • https://pubmed.ncbi.nlm.nih.gov/15231645/

Chemical Information

Molecular Weight 320.3 Formula

C13H16N6O4
CAS No. 35943-35-2 SDF Download Triciribine (API-2) SDF
Synonyms NSC 154020, VD-0002, vqd-002, TCN
Smiles CN1C2=NC=NC3=C2C(=CN3C4C(C(C(O4)CO)O)O)C(=N1)N

Storage and Stability

Storage (From the date of receipt)

In vitro
Batch:

DMSO : 64 mg/mL ( (199.81 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 16 mg/mL

Water : Insoluble


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