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Triciribine

现货
Catalog No.
A8541
Akt抑制剂
组合的产品项目
规格价格库存 数量
5mg
¥ 850.00
现货
10mg
¥ 1,200.00
现货
50mg
¥ 4,000.00
现货

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Background

Triciribine is an inhibitor of DNA synthesis for Akt and HIV-1 with IC50 values of 130 nM and 20 nM, respectively. [1,2]
Protein kinase B (PKB), also known as Akt, is a serine/threonine-specific protein kinase that plays a key role in multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription and cell migration. Once PH domain of Akt bind phospholipids ,the activated Akt can then go on to activate or deactivate its myriad substrates via its kinase activity. e.g. Nuclear Factor-kB, Bcl-2 family proteins and murine double minute 2 (MDM2).[3] Studies show that tumor cells have constantly active Akt depending on Akt for survival [4], so Akt inhibitors may treat cancers.
Triciribine, also known as API-2, suppresses the phosphorylation level and kinase activity of Akt, result in induce apoptosis and cell growth in cancer cell. Triciribine can specifically inhibit the most common astrocytic tumor cells inhibitory efficiency was very low (13.6 mM [5] GI50). Triciribine can inhibit HIV-1, IC50 20 nM. The amount of inhibition of 0.1 M can produce >90% ratio, dosage of 5 M could completely inhibit coenocytic. In the same cell line cytotoxicity test results showed when the concentration of Triciribine for the selective index of 46 M to 2250 using HIV-1 infected CEM-SS, H9, and B and U1 persistent infection of H9III cells of p24 core antigen, Triciribine can significantly inhibit HIV-1 induced generation, reverse transcriptase and the generation of infectious virus, this inhibition is dose dependent characteristics [6]. Triciribine inhibits human prostate cancer cell line PC-3 in the Akt 308 bit acid and serine 473 phosphorylation and Akt activity. Triciribine make PC-3 cells more sensitive to apoptosis induced by TRAIL- and anti-CD95, but to DNA damage caused by chemotherapy is still resistance [7]. Triciribine also can selectively inhibit Akt1, Akt2, and Akt3 without inhibiting known upstream activators, PDK1 and PI3K, of Akt. Additionally, Triciribine has antineoplastic and antiviral activity at low micromolar and submicromolar concentrations, and has been demonstrated to inhibit incorporation of amino acids into proteins and purine nucleotide synthesis.
Reference:
1 Gursel DB, et al. “Control of proliferation in astrocytoma cells by the receptor tyrosine kinase/PI3K/AKT signaling axis and the use of PI-103 and TCN as potential anti-astrocytoma therapies”. Nero Oncol, 2011, 13(6), 610-621.
2 Kucera LS, et al, AIDS Res Hum Retroviruses, 1993, 9(4), 307-314.
3 Song G, Ouyang G, Bao S. "The activation of Akt/PKB signaling pathway and cell survival". J. Cell. Mol. Med, 2005, 9 (1): 59-71.
4 Lindhurst MJ, Sapp JC, Teer JK, Johnston JJ, Finn EM, Peters K et al. "A mosaic activating mutation in AKT1 associated with the Proteus syndrome". N. Engl. J. Med, 2011, 365 (7): 611-9.
5 Gursel DB, et al, Nero Oncol, 2011, 13(6), 610-621.
6 Dieterle A, et al, Int J Cancer , 2009, 125(4), 932-941.
7 Yang L, et al, Cancer Res, 2004, 64(13), 4394-4399.

文献引用

1. Li Y, Yang Y, et al. "Astragaloside IV reduces neuronal apoptosis and parthanatos in ischemic injury by preserving mitochondrial hexokinase-II." Free Radic Biol Med. 2019 Feb 1;131:251-263. PMID:30502455
2. Du Q, Zhang S, et al. "Astragaloside IV Inhibits Adipose Lipolysis and Reduces Hepatic Glucose Production via Akt Dependent PDE3B Expression in HFD-Fed Mice." Front Physiol. 2018 Jan 23;9:15. PMID:29410630
3. Qun Liu, Fei-Ge Zhang, et al. "Ginsenoside Rg1 Inhibits Glucagon-Induced Hepatic Gluconeogenesis through Akt-FoxO1 Interaction."Theranostics 2017; 7(16):4001-4012.
4. Song J, Li Y, et al. "Mangiferin protects mitochondrial function by preserving mitochondrial hexokinase-II in vessel endothelial cells."Biochim Biophys Acta. 2017 Jul;1863(7):1829-1839. PMID:28478227
5. Yang YL, Li J, et al. "Ginsenoside Rg5 increases cardiomyocyte resistance to ischemic injury through regulation of mitochondrial hexokinase-II and dynamin-related protein 1." Cell Death Dis. 2017 Feb 23;8(2):e2625. PMID:28230856

Chemical Properties

StorageStore at -20°C
M.Wt320.3
Cas No.35943-35-2
FormulaC13H16N6O4
Solubility≥118.4mg/mL in DMSO
Chemical Name(2R,3R,4S,5R)-2-(3-amino-5-methyl-1,4,5,6,8-pentaazaacenaphthylen-1(5H)-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol
SDFDownload SDF
Canonical SMILES[H][C@](N1C(N=C([H])N=C2N(C([H])([H])[H])N=C3N([H])[H])=C2C3=C1[H])([C@]4([H])O[H])O[C@@](C([H])([H])O[H])([H])[C@@]4([H])O[H]
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验 [1-3]:

细胞系

星形细胞瘤细胞,HIV-1,PC-3细胞

溶解方法

该化合物在DMSO中的溶解度大于118.4mg/mL。若获取更高浓度的溶液,可在37℃下孵育10分钟,随后在超声波浴中摇匀。-20℃以下可储存数月。

反应条件

IC50: 130 nM (Akt), IC50: 0.02-0.46 μM (HIV-1/2)

应用

Triciribine(1-10 μM)抑制Nf1和Trp53突变型星形细胞瘤细胞中的细胞生长。Triciribine(100 μM)抑制Akt和p70S6K的磷酸化至基础水平。Triciribine不完全抑制WHO II K1861-10细胞系,GI50值为1.7 μM。在较低的GI50值(0.4-1.1 μM)下,Triciribine能够更大程度地抑制肿瘤细胞系(KR158、KR130和SF295)。Triciribine抑制HIV-1,IC50为20 nM。Triciribine(5 μM)完全抑制合胞体形成。在HIV-1急性感染的CEM-SS、H9和持续感染的H9IIIB和U1细胞中,Triciribine以剂量依赖性方式显著抑制HIV-1诱导的p24核心抗原产生、逆转录酶和感染性病毒产生。Triciribine抑制人前列腺癌细胞系PC-3中Akt蛋白Thr308和Ser473的磷酸化和Akt活性。

动物实验 [4]:

动物模型

携带OVCAR3、OVCAR8和PANC1肿瘤的裸鼠

给药剂量

腹腔注射,1 mg/kg/day,7 days

应用

Triciribin抑制OVCAR3、OVCAR8和PANC1肿瘤生长。

注意事项

由于实验环境的不同,实际溶解度可能与理论值略有不同,请测试室内所有化合物的溶解度。

References:

[1]. Gürsel D B, Connell-Albert Y S, Tuskan R G, et al. Control of proliferation in astrocytoma cells by the receptor tyrosine kinase/PI3K/AKT signaling axis and the use of PI-103 and TCN as potential anti-astrocytoma therapies[J]. Neuro-oncology, 2011, 13(6): 610-621.

[2]. KUCERA L S, IYER N P, PUCKETT S H, et al. Activity of triciribine and triciribine-5′-monophosphate against human immunodeficiency virus types 1 and 2[J]. AIDS research and human retroviruses, 1993, 9(4): 307-314.

[3]. Dieterle A, Orth R, Daubrawa M, et al. The Akt inhibitor triciribine sensitizes prostate carcinoma cells to TRAIL‐induced apoptosis[J]. International journal of cancer, 2009, 125(4): 932-941.

[4]. Yang L, Dan H C, Sun M, et al. Akt/protein kinase B signaling inhibitor-2, a selective small molecule inhibitor of Akt signaling with antitumor activity in cancer cells overexpressing Akt[J]. Cancer research, 2004, 64(13): 4394-4399.

生物活性

Description Triciribine是DNA合成的抑制剂,对Akt和HIV-1的IC50值分别为130 nM和20 nM。
靶点 HIV-1 Akt        
IC50 20 nM 130 nM        

质量控制

化学结构

Triciribine

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