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PI-103I类PI3K、mTOR和DNA-PK抑制剂

PI-103

产品编号:A2067
ApexBio 的所有产品仅用作科研,我们不为任何个人用途提供产品和服务
规格 单价 库存 订购数量
10mM (in 1mL DMSO) ¥900.00 现货
5mg ¥840.00 现货
25mg ¥2,400.00 现货
100mg ¥6,800.00 现货

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Sample solution is provided at 25 µL, 10mM.

引用文献

1. Sabha N, Volpatti JR, et al. "PIK3C2B inhibition improves function and prolongs survival in myotubular myopathy animal models." J Clin Invest. 2016 Sep 1;126(9):3613-25. PMID:27548528

质量控制

化学结构

PI-103

相关生物数据

PI-103

相关生物数据

PI-103

相关生物数据

PI-103

PI-103 Dilution Calculator

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PI-103 Molarity Calculator

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化学性质

CAS号 371935-74-9 SDF Download SDF
化学名 3-(4-morpholin-4-ylpyrido[2,3]furo[2,4-b]pyrimidin-2-yl)phenol
SMILES C1COCCN1C2=NC(=NC3=C2OC4=C3C=CC=N4)C5=CC(=CC=C5)O
分子式 C19H16N4O3 分子量 348.36
溶解度 ≥21.9mg/mL in DMSO 储存条件 Store at -20°C
物理性状 A solid 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。

生物活性

描述 PI-103是PI3K的多靶点抑制剂,作用于p110α/β/δ/γ,IC50值为2 nM/3 nM/3 nM/15 nM,对mTOR/DNA-PK的作用较弱,IC50值为30 nM/23 nM。
靶点 p110α p110β p110δ p110γ mTOR DNA-PK
IC50 2 nM 3 nM 3 nM 15 nM 30 nM 23 nM

实验操作

细胞实验[1]:

细胞系

A549和H460 细胞

溶解方法

该化合物在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。

反应条件

A549细胞:72小时,2 μM;H460细胞:72小时,0.5 μM

实验结果

使用2 μM PI-103与A549细胞孵育72小时,诱导细胞数量减少大约60%。与A549细胞相比,H460细胞对低剂量的PI-103高度敏感。0.5 μM PI-103处理H460细胞72小时产生大约60%的抑制效果。结果显示,使用相应浓度的PI-103处理A549和H460细胞72小时,PI-103以剂量依赖性的方式诱导生长抑制。

动物实验[2]:

动物模型

注射37-31E-F3细胞的FVB/N野生型小鼠

剂量

腹膜内注射,10 mg/kg,每天

实验结果

与DMSO处理的小鼠相比,PI-103处理显著促进体内肿瘤生长,它通过部分抑制Akt和S6核糖体蛋白磷酸化发挥作用。PI-103处理小鼠的肿瘤中含有更高水平的细胞周期蛋白D1和更多的增殖细胞,正如Ki67阳性细胞中的数量。PI-103处理的肿瘤凋亡率较低。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。

References:

[1] Zou Z Q, Zhang X H, Wang F, et al. A novel dual PI3Kalpha/mTOR inhibitor PI-103 with high antitumor activity in non-small cell lung cancer cells. Int J Mol Med, 2009, 24(1): 97-101.

[2] López‐Fauqued M, Gil R, Grueso J, et al. The dual PI3K/mTOR inhibitor PI‐103 promotes immunosuppression, in vivo tumor growth and increases survival of sorafenib-treated melanoma cells. International journal of cancer, 2010, 126(7): 1549-1561.

研究更新

1. PI-103 sensitizes acute myeloid leukemia stem cells to daunorubicin-induced cytotoxicity. Med Oncol. 2013 Mar;30(1):395. doi: 10.1007/s12032-012-0395-5. Epub 2013 Jan 19.
Abstract
PI-103 is a PI3K/Akt/mTOR signaling pathway inhibitor that induces apoptosis in LSCs. The combination of PI-103 and DNR synergistically induces apoptosis in LSCs without affecting hematopoietic stem cells, where PI-103 sensitizes LSCs to DNR-induced cytotoxicity.
2. Chloroquine overcomes resistance of lung carcinoma cells to the dual PI3K/mTOR inhibitor PI103 by lysosome-mediated apoptosis. Anticancer Drugs. 2013 Jan;24(1):14-9. doi: 10.1097/CAD.0b013e32835a36db.
Abstract
The co-treatment of PI103, a PI3K/mTOR inhibitor, and CQ induces lysosome-mediated apoptosis in lung carcinoma cells, where PI103 increases lysosomal volume and function with its resistance reduced by CQ.
3. Arsenic disulfide synergizes with the phosphoinositide 3-kinase inhibitor PI-103 to eradicate acute myeloid leukemia stem cells by inducing differentiation. Carcinogenesis. 2011 Oct;32(10):1550-8. doi: 10.1093/carcin/bgr176. Epub 2011 Jul 29.
Abstract
Propidium iodide-103 not only effectively inhibited PI3K/AKT/mTOR pathway activated by As(2)S(2) but also synergized with As(2)S(2) to eradicate non-APL LSCs, promote their differentiation and reduce their repopulation.
4. A dual PI3K/mTOR inhibitor, PI-103, cooperates with stem cell-delivered TRAIL in experimental glioma models. Cancer Res. 2011 Jan 1;71(1):154-63. doi: 10.1158/0008-5472.CAN-10-1601. Epub 2010 Nov 17.
Abstract
PI-103 is a PI3-kinase/mTOR inhibitor that exhibits anti-glioma activity through inhibiting tumor cell proliferation and invasion, arresting G(0)-G(1) phases of cell cycle and attenuating tumor growth. The combined therapy of PI-103 and S-TRAIL showed enhanced tumor volume reduction.
5. PI-103 and sorafenib inhibit hepatocellular carcinoma cell proliferation by blocking Ras/Raf/MAPK and PI3K/AKT/mTOR pathways. Anticancer Res. 2010 Dec;30(12):4951-8.
Abstract
The anti-proliferative activities of sorafenib, PI-103 and their combination in Huh7 have been demonstrated.

产品描述

PI-103是一种有效的和选择性的I类PI3K、mTOR和DNA-PK抑制剂,作用于p110α、p110β、p110δ、p110γ、mTOR和DNA-PK,IC50值分别为2、3、3、15、30和23 nM[1]。

PI-103在各种癌细胞系中具有有效的抗增殖活性,如前列腺癌,卵巢癌和胶质母细胞瘤。在U87MG、IGROV-1、DETROIT-562、PC3、SKOV-3和HUVEC细胞中,PI-103的GI50值分别为0.14、0.06、0.13、0.10、0.12和0.08 μM。在U87MG细胞中,PI-103处理2小时后对PI3K途径的各种磷酸化蛋白标志物具有抑制效应,作用于p-AKTSer473、p-AKTThr308、p-GSK3βSer9、p-p70S6KThr421/Ser424和p-S6RPSer235/Ser236,IC50值分别为15、36、111、106和105 nM[1]。

参考文献:
[1] Raynaud F I, Eccles S A, Patel S, et al.  Biological properties of potent inhibitors of class I phosphatidylinositide 3-kinases: from PI-103 through PI-540, PI-620 to the oral agent GDC-0941. Molecular cancer therapeutics, 2009, 8(7): 1725-1738.