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PF-543

现货
Catalog No.
A3717
SphK1选择性抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,050.00
现货
5mg
¥ 1,100.00
现货
10mg
¥ 1,950.00
现货
50mg
¥ 7,000.00
Ship with 10-15 days
200mg
¥ 18,000.00
Ship with 10-15 days

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Background

PF-543 is a novel and cell-permeant inhibitor of Sphingosine kinase (SphK1) with IC50 value of 3.6 nM [1],

SphK1 is a kinase that phosphorylates sphingosine to sphingosine-1-phosphate (SIP). SphK1 is normally a cytosolic protein but can be recruited to the membrane to conduct its activity. It is the major source of production of S1P which promotes cell growth, survival and migration, and also regulate lymphocyte trafficking.

Biochemical study has identified that SphK1 was a sphingosine-competitive inhibitor but not ATP-competitive [1]. In 1483 head and neck carcinoma cell cultures expressing high levels of SphK1 and with an unusually high rate of S1P production, pretreatment of PF-543 for 1 hr decreased the level of endogenous S1P by 10-fold with a proportional increase in the level of sphingosine. It indicated a significant inhibition of SphK1 BY pf-543. However, specific inhibition of SphK1 had no effect on the proliferation and survival of 1483 cell cultures, despite a dramatic change in the cellular S1P/sphingosine rate [1].

The inhibitory activity of PF-543 was also examined ex vivo in human whole blood. Human whole blood with high SphK1 activity was prepared, which was able to quickly convert C17-sphingosine to C17-S1P. PF-543 treatment showed that PF-543 was a potent inhibitor of SphK1, capable of blocking >90% C17-S1P formation [1].

Reference:
[1] Schnute M E et al. , Modulation of cellular S1P levels with a novel, potent and specific inhibitor of sphingosine kinase-1. Biochem J. 2012, 444(1): 79-88.

文献引用

1. Wang S, Liang Y, et al. "Triple Negative Breast Cancer Depends on Sphingosine Kinase 1 (SphK1)/Sphingosine-1-Phosphate (S1P)/Sphingosine 1-Phosphate Receptor 3 (S1PR3)/Notch Signaling for Metastasis." Med Sci Monit. 2018 Apr 1;24:1912-1923. PMID:29605826

Chemical Properties

Physical AppearanceA yellow oil
StorageStore at -20°C
M.Wt465.6
Cas No.1415562-82-1
FormulaC27H31NO4S
SynonymsPF543; PF 543
Solubility≥23.3 mg/mL in DMSO, ≥51 mg/mL in EtOH with ultrasonic and warming, <2.72 mg/mL in H2O
Chemical Name[(2R)-1-[[4-[[3-(benzenesulfonylmethyl)-5-methylphenoxy]methyl]phenyl]methyl]pyrrolidin-2-yl]methanol
SDFDownload SDF
Canonical SMILESCC1=CC(=CC(=C1)OCC2=CC=C(C=C2)CN3CCCC3CO)CS(=O)(=O)C4=CC=CC=C4
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

1483头颈癌细胞

溶解方法

该化合物在DMSO中的溶解度大于23.3 mg/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

1 μM,1 h

应用

在1483头颈癌细胞中,PF-543预处理1小时剂量依赖性消耗细胞内S1P含量,EC50浓度为8.4 nM,同时伴随着鞘氨醇的细胞内水平升高。PF-543对其他几种癌细胞系的生长没有影响。在人全血中,PF-543抑制S1P形成,IC50为26.7 nM。

动物实验 [2]:

动物模型

肺动脉高压小鼠低氧模型

给药剂量

腹腔注射,10 mg/kg,24 h

应用

在肺动脉高压小鼠低氧模型中,PF-543对血管重塑无影响,但降低右心室肥大。在小鼠中,给药10 mg/kg PF-543 24小时降低了肺血管中的SK1表达。

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]. Schnute M E, McReynolds M D, Kasten T, et al. Modulation of cellular S1P levels with a novel, potent and specific inhibitor of sphingosine kinase-1[J]. Biochemical Journal, 2012, 444(1): 79-88.

[2]. MacRitchie N, Volpert G, Al Washih M, et al. Effect of the sphingosine kinase 1 selective inhibitor, PF-543 on arterial and cardiac remodelling in a hypoxic model of pulmonary arterial hypertension[J]. Cellular signalling, 2016, 28(8): 946-955.

生物活性

Description PF-543是一种新型的细胞渗透性SphK1抑制剂,其Ki值为3.6 nM。
靶点 SphK1          
IC50 3.6 nM (Ki)          

质量控制

化学结构

PF-543

相关生物数据

PF-543