PF-543 Citrate |
| Catalog No.GC16352 |
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1415562-83-2
Sample solution is provided at 25 µL, 10mM.
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PF-543 Citrate (Sphingosine Kinase 1 Inhibitor II Citrate) is a novel cell-permeant inhibitor of SPHK1 with a Ki of 4.3 nM and more than 100-fold selectivity for SPHK1 over SPHK2.
PF-543 Citrate (Sphingosine Kinase 1 Inhibitor II Citrate) is a novel selective sphingosine-competitive inhibitor of SphK1 that is over 1000-fold more potent in suppressing 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-fold selective for SphK1 over the SphK2 isoform. In 1483 head and neck carcinoma cells, which are characterized by high levels of SphK1 expression and an unusually high rate of S1P production, PF-543 decreases the level of endogenous S1P 10-fold with a proportional increase in the level of sphingosine[1]. PF-543 inhibits SphK1 in the in vitro enzyme assay with an IC50 value of 2.0±0.6 nM and is able to inhibit the enzyme >95% at a concentration of 20 nM[1]. PF-543 bounds in a bent conformation analogous to that expected of a bound sphingosine substrate but with a rotated head group[2].
Administration of the potent sphingosine kinase 1 inhibitor, PF-543 Citrate (Sphingosine Kinase 1 Inhibitor II Citrate) 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[3].
References:
[1]. Schnute ME, et al. Modulation of cellular S1P levels with a novel, potent and specific inhibitor of sphingosine kinase-1. Biochem J. 2012 May 15;444(1):79-88.
[2]. 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 model of pulmonary arterial hypertension. Cell Signal. 2016 Aug;28(8):946-55.
Cell experiment: | 1483, Jurkat andU937 cells are grown in 96-well plates in 100 μL of medium with PF-543 or DMSO vehicle (0.01%) at 37°C in an humidified incubator in the presence of 5% CO2. The cell growth and viability is measured using the CellTiter-Glo Assay by quantifying luminescence proportional to the amount of ATP present[1]. |
Animal experiment: | Mice: Two month old female mice (C57BL/6 J) are injected via the tail vein with RB-005 or PF-543 (10 or 30 mg/kg) dissolved in vehicle (PBS). 20 μL blood is withdrawn via tail vein bleeds at 15 min, 30 min, 1 h, 4 h, 6 h and 24 h following drug administration. Drug concentration is determined by MS analysis[3]. |
References: [1]. Schnute ME, et al. Modulation of cellular S1P levels with a novel, potent and specific inhibitor of sphingosine kinase-1. Biochem J. 2012 May 15;444(1):79-88. | |
| Cas No. | 1415562-83-2 | SDF | |
| Chemical Name | [(2R)-1-[[4-[[3-(benzenesulfonylmethyl)-5-methylphenoxy]methyl]phenyl]methyl]pyrrolidin-2-yl]methanol;2-hydroxypropane-1,2,3-tricarboxylic acid | ||
| Canonical SMILES | CC1=CC(=CC(=C1)OCC2=CC=C(C=C2)CN3CCCC3CO)CS(=O)(=O)C4=CC=CC=C4.C(C(=O)O)C(CC(=O)O)(C(=O)O)O | ||
| Formula | C33H39NO11S | M.Wt | 657.73 |
| Solubility | ≥ 89.4 mg/mL in DMSO, ≥ 28.33 mg/mL in EtOH with ultrasonic and warming, ≥ 51.8 mg/mL in Water with ultrasonic and warming | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.5204 mL | 7.6019 mL | 15.2038 mL |
| 5 mM | 0.3041 mL | 1.5204 mL | 3.0408 mL |
| 10 mM | 0.152 mL | 0.7602 mL | 1.5204 mL |
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
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Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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