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PF-543
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
PF-543图片
CAS NO:1415562-82-1
包装与价格:
包装价格(元)
2 mg电议
5 mg电议
10 mg电议
50 mg电议
1 mL*10 mM(in DMSO)电议

产品名称
PF 543
Sphingosine Kinase 1 Inhibitor II
产品介绍
PF543是一种选择性可逆和鞘氨醇竞争性SPHK1抑制剂,可诱导细胞凋亡、坏死和自噬。它对SPHK1的选择性是 SPHK2 的 100 倍以上。它还抑制全血中 1-磷酸鞘氨醇形成,IC50为 26.7 nM。

产品描述

PF-543, a novel sphingosine-competitive inhibitor of SphK1, inhibits SphK1 with IC50 and Ki of 2.0 nM and 3.6 nM.

体外活性

PF543 is a cell-permeable hydroxyl methylpyrrolidine compound that inhibits SphK-1/SphK1-catalyzed sphingosine phosphorylation in a reversible and sphingosine-competitive manner, exhibiting no affinity toward S1P receptors and much reduced inhibitory activity against Sphk2 (6.8% inhibition at 10 μM) or 46 other lipid and portein kinases (IC50 >10 μM). In the SphK1-overexpression 1483 head and neck carcinoma cells, PF-543 decreases the level of endogenous S1P 10-fold with a proportional increase in the level of sphingosine. PF-543 binds SphK1 reversibly (k off t1/2=8.5 min) and with high affinity and the binding constant (Kd) is 5 nM. PF543 had no effect on the proliferation and survival of 1483, A549, LN229, Jurkat, U937 and MCF-7 cells, despite a dramatic change in the cellular S1P/sphingosine ratio. PF-543 is effective as a potent inhibitor of S1P formation in whole blood, indicating that the SphK1 isoform of sphingosine kinase is the major source of S1P in human blood. [1]

体内活性

Administration of the potent sphingosine kinase 1 inhibitor, PF-543 in a mouse hypoxic model of pulmonary hypertension has no effect on vascular remodelling but reduces right ventricular hypertrophy. Administration of 10 mg/kg PF-543 for 24 h to mice induces a decrease in SK1 expression in pulmonary vessels[2].

激酶实验

FITC-S1P quantification/Caliper assay: A 384-well format of the SphK enzyme assay based on separation of FITC-S1P from unreacted FITC-sphingosine substrate using a microfluidic capillary electrophoresis mobility-shift system is developed. Briefly, 3 nM SphK1–His6 is incubated with 1 μM FITC-sphingosine, 20 μM ATP and 10 μM compound (a final concentration of DMSO of 2 %) in a buffer containing 100 mM Hepes (pH 7.4), 1 mM MgCl2,0.01% Triton X-100, 10% glycerol, 100 μM sodium orthovanadate and 1 mM DTT for 1 h in a 384-well Matrical MP-101-1-PP plate. Reaction mixtures (10 μL) are quenched by the addition of 20 μL of 30 mM EDTA and 0.15% Coating Reagent-3 in 100 mM Hepes, and a small aliquot of each reaction (a few nanolitres) is analysed in the Caliper LabChip 3000 instrument under -1.5 psi (psi=6.9 kPa) pressure, a downstream voltage of -1900 V and a sip time of 0.2 s. Phosphorylated fluorescent product and unphosphorylated fluorescent substrate appeared as distinctive peaks and are quantified using the Caliper data.

细胞实验

CellTiter-Glo Assay (Only for Reference)

Cas No.

1415562-82-1

分子式

C27H31NO4S

分子量

465.61

别名

PF 543;Sphingosine Kinase 1 Inhibitor II

储存和溶解度

H2O:<1 mgml
DMSO:93 mg/mL (199.74 mM)
Ethanol:93 mg/mL (199.74 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years