PF-543-Citrate-Sphingosine-Kinase-1-Inhibitor-II-Citrate-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEPF-543 CitrateCat. No.: HY-15425ACAS No.: 1415562-83-2Synonyms: Sphingosine Kinase 1 Inhibitor II (Citrate)分式: CHNOS分量: 657.73作靶点: SPHK作通路: Immunology/Inflammation储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1

2、month溶解性数据体外实验 DMSO : 100 mg/mL (152.04 mM)H2O : 50 mg/mL (76.02 mM; Need ultrasonic)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 1.5204 mL 7.6019 mL 15.2038 mL5 mM 0.3041 mL 1.5204 mL 3.0408 mL10 mM 0.1520 mL 0.7602 mL 1.5204 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制

3、储备液，并请注意储备液的保存式和期限。体内实验请根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您现现配，当天使；澄的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (3.80 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)1/3

4、Master of Small Molecules 您边的抑制剂师www.MedChemESolubility: 2.5 mg/mL (3.80 mM); Clear solution3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (3.80 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 PF-543 Citrate新颖的可渗透细胞的SPHK1抑制剂，Ki值为4.3 nM。对SPHK1的选择性SPHK2的100倍以上。IC50 & Target Ki: 3.6 nM (SPHK1) 1体外研

5、究 PF-543 is a novel selective sphingosine-competitive inhibitor of SphK1 that is over 1000-fold more potent insuppressing cellular S1P formation than DMS and SKI-2, commonly used pharmacological tools for SphK.PF-543 inhibits SphK1 with a Ki of 3.6 nM, is sphingosine-competitive and is more than 100

6、-fold selective forSphK1 over the SphK2 isoform. In 1483 head and neck carcinoma cells, which are characterized by highlevels of SphK1 expression and an unusually high rate of S1P production, PF-543 decreases the level ofendogenous S1P 10-fold with a proportional increase in the level of sphingosine

7、 1. PF-543 inhibits SphK1 inthe in vitro enzyme assay with an IC50 value of 2.00.6 nM and is able to inhibit the enzyme 95% at aconcentration of 20 nM 1. PF-543 bounds in a bent conformation analogous to that expected of a boundsphingosine substrate but with a rotated head group 2.体内研究 Administratio

8、n of the potent sphingosine kinase 1 inhibitor, PF-543 in a mouse hypoxic model of pulmonaryhypertension has no effect on vascular remodelling but reduces right ventricular hypertrophy. Administrationof 10 mg/kg PF-543 for 24 h to mice induces a decrease in SK1 expression in pulmonary vessels 3.PROT

9、OCOLCell Assay 1 1483, Jurkat andU937 cells are grown in 96-well plates in 100 L of medium with PF-543 or DMSO vehicle(0.01%) at 37C in an humidified incubator in the presence of 5% CO2. The cell growth and viability ismeasured using the CellTiter-Glo Assay by quantifying luminescence proportional t

10、o the amount of ATPpresent 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice: Two month old female mice (C57BL/6 J) are injected via the tail vein with RB-005 or PF-543 (10 or 30Administration 3 mg/kg) dissolved in vehicle (PBS). 20 L blood

11、is withdrawn via tail vein bleeds at 15 min, 30 min, 1 h, 4 h, 6h and 24 h following drug administration. Drug concentration is determined by MS analysis 3.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Schnute ME, et al. Modulation of cel

12、lular S1P levels with a novel, potent and specific inhibitor of sphingosine kinase-1. Biochem J. 2012May 15;444(1):79-88.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemE2. Wang J, et al. Crystal Structure of Sphingosine Kinase 1 with PF-543. ACS Med Chem Lett. 2014 Oct 27;5(12):1329-33.3. MacRitchie N, et al. Effect of the sphingosine kinase 1 selective inhibitor, PF-543 on arterial and cardiac remodelling in a hypoxic modelof pulmonary arterial hypertension. Cell Signal. 2016 Aug;28(8):946-55.McePdfHeight