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PX-478 2HCl

现货
Catalog No.
B6004
HIF-1α抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,000.00
现货
5mg
¥ 800.00
现货
10mg
¥ 1,400.00
现货
50mg
¥ 3,500.00
现货
100mg
¥ 5,500.00
现货

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Background

PX-478 2HCl, also called PX-478, is an experimental HIF-1α inhibitor. It inhibited HIF-1α protein at multiple levels in cancer cell lines under normoxia and hypoxia with an IC50 value of ~20-30 μM [1].

Hypoxia-inducible transcription factor HIF-1α activates target genes involved in glycolysis, erythropoiesis and angiogenesis. HIF-1α also regulates the expression of genes coding for apoptotic pathway, growth factors/receptors, cell cycle regulators, metastasis and invasiveness [1].

Under normoxic condition, the IC50 for PX-478 to inhibit HIF-1α in PC3 cells was 20-25 μmol/L, whereas the IC50 for PX-478 to inhibit HIF-1α in the DU 145 cells was ~40-50 μmol/L. in both DU 145 and PC3 cells, 1-hr hypoxia significantly upregulated HIF-1α protein. But the pretreatment with PX-478 for 20 hr under normoxia before 1-hr hypoxia attenuated the accumulation of HIF-1α induced by the 1-hr hypoxia. In PC3 cells, pretreatment with 20 μmol/L PX-478 before hypoxia inhibited HIF-1α by 40% compared to treatment with hypoxia alone. In DU 145 cells, pretreatment with 50 μmol/L PX-478 before hypoxia inhibited HIF-1α by 35% compared to treatment with hypoxia alone [1].

In nu/nu mice with C6 reporter xenografts, treatment with PX-478 at a dose of 30 mg/kg p.o. for 2 consecutive days prevented the transcriptional activity of HIF-1 in central ischemic regions of C6 tumors [2].

References:
[1].  Palayoor ST, Mitchell JB, Cerna D, et al. PX-478, an inhibitor of hypoxia-inducible factor-1α, enhances radiosensitivity of prostate carcinoma cells. International journal of cancer, 2008, 123(10): 2430-2437.
[2].  Schwartz DL, Powis G, Thitai-Kumar A, et al. The selective hypoxia inducible factor-1 inhibitor PX-478 provides in vivo radiosensitization through tumor stromal effects. Molecular cancer therapeutics, 2009, 8(4): 947-958.

Chemical Properties

StorageStore at -20°C
M.Wt394.12
Cas No.685898-44-6
FormulaC13H20Cl4N2O3
Solubility≥19.7mg/mL in DMSO
Chemical Name(S)-4-(2-amino-2-carboxyethyl)-N,N-bis(2-chloroethyl)aniline oxide dihydrochloride
SDFDownload SDF
Canonical SMILESClCC[N+](C1=CC=C(C[C@@](N)([H])C(O)=O)C=C1)([O-])CCCl.Cl.Cl
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]:

细胞系

DU145细胞

制备方法

在DMSO中的溶解度大于19.7 mg/mL。若配制更高浓度的溶液,一般步骤如下:请将试管置于37 °C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 °C可放置数月。

反应条件

25 μM;18小时

实验结果

在缺氧条件下,给予PX-478,于18小时后可以增加DU145细胞的放射敏感性,但不会显著影响HIF-1α蛋白水平。

动物实验 [2]:

动物模型

携带C6报告基因异种移植瘤的裸鼠

给药剂量

30 mg/kg;口服给药;持续2天

实验结果

在携带C6报告基因异种移植瘤的裸鼠中,PX-478治疗(30 mg/kg;口服给药;持续2天)抑制C6肿瘤中心缺血区域HIF-1的转录活性。

注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

[1]. Palayoor ST, Mitchell JB, Cerna D, et al. PX-478, an inhibitor of hypoxia-inducible factor-1α, enhances radiosensitivity of prostate carcinoma cells. International journal of cancer, 2008, 123(10): 2430-2437.

[2]. Schwartz DL, Powis G, Thitai-Kumar A, et al. The selective hypoxia inducible factor-1 inhibitor PX-478 provides in vivo radiosensitization through tumor stromal effects. Molecular cancer therapeutics, 2009, 8(4): 947-958.

质量控制

化学结构

PX-478 2HCl