| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| ln Vitro |
SK1 expression is eliminated at nM concentrations when PASM cells are treated with PF-543 Citrate (10-1000 nM) for 24 hours [2]. Caspases-3/7 are activated when treated with PF-543 Citrate (0.1–10 μM) for 24 hours in PASM cells [2]. With an IC 50 of 1.0 nM, PF-543 Citrate suppresses the production of C17-S1P in 1483 cells[1]. When PF-543 Citrate inhibited SphK1, intracellular S1P levels were depleted in a dose-dependent manner with an EC50 value of 8.4 nM, while intracellular sphingosine levels increased in 1483 cells concurrently. 1483 cells' endogenous S1P levels were tenfold decreased and sphingosine levels increased following an hour-long treatment with 200 nM PF-543 Citrate [1].
In vitro, PF-543 Citrate inhibits SphK1 with an IC₅0 of 2 nM and a Ki of 3.6 nM. It is sphingosine-competitive and shows more than 100-fold selectivity for SphK1 over SphK2. The compound is the most potent SphK1 inhibitor described to date and is a potent inhibitor of S1P formation in whole blood. Detailed cellular activity data are available in the literature. |
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| ln Vivo |
While PF-543 Citrate (1 mg/kg; i.p.; every other day; for 21 days; female C57BL/6 J mice) decreased right ventricular hypertrophy, it had no effect on vascular remodeling. Protection entails elevated expression of the antioxidant nuclear protein Nrf-2 and decreased expression of p53 [2]. T1/2 in blood samples was 1.2 hours after mice were first given PF-543 Citrate at doses of 10 mg/kg or 30 mg/kg for a duration of 24 hours. Mice given 10 mg/kg PF-543 Citrate for a full day showed a reduction in SK1 expression in their pulmonary arteries [2].
In vivo activity data for PF-543 Citrate are not extensively documented. As a potent and selective SphK1 inhibitor, the compound is expected to modulate S1P signaling in vivo. It is used as a research tool for dissecting specific roles of SphK1-driven S1P signaling. Further in vivo studies would be needed to characterize its pharmacokinetic and efficacy profile. |
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| Enzyme Assay |
The in vitro enzyme assay for SphK1 uses recombinant human SphK1 enzyme and sphingosine substrate with ATP. Kinase activity is measured by quantifying the production of S1P using radiolabeled ATP ([32P]-ATP), mass spectrometry, or fluorescence-based methods. IC₅0 and Ki values are calculated from dose-response curves. Selectivity against SphK2 and other kinases is assessed using similar assays.
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| Cell Assay |
Western Blot Analysis[2]
Cell Types: Human pulmonary arterial smooth muscle (PASM) cells Tested Concentrations: 10 nM, 100 nM, 1000 nM Incubation Duration: 24 hrs (hours) Experimental Results: Abolished SK1 expression at nM concentrations. Apoptosis Analysis[2] Cell Types: Human pulmonary arterial smooth muscle (PASM) cells Tested Concentrations: 0.1 μM, 1 μM, 10 μM Incubation Duration: 24 hrs (hours) Experimental Results: Induced caspase-3/7 activity in cultured human pulmonary smooth muscle cells. For in vitro cell-based assays, cells are cultured and treated with PF-543 Citrate at various concentrations. S1P levels in cell lysates or culture media are measured by LC-MS or ELISA. Cell proliferation, survival, or migration may be assessed depending on the cell type. SphK1 inhibition is confirmed by measuring the reduction in S1P production. Experiments are typically performed in triplicate with appropriate positive and negative controls. |
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| Animal Protocol |
Animal/Disease Models: Female C57BL/6 J mice (7-12 week-old) with hypoxic-induced pulmonary arterial hypertension[2]
Doses: 1 mg/kg Route of Administration: intraperitoneal (ip)injection; every second day; for 21 days Experimental Results: decreased right ventricular hypertrophy. The protection involves a reduction in the expression of p53 (that promotes cardiomyocyte death) and an increase in the expression of anti-oxidant nuclear factor Nrf-2. In vivo animal studies for PF-543 Citrate would typically involve mouse models where SphK1/S1P signaling is implicated (such as inflammation, cancer, or fibrosis models). The compound is administered via intraperitoneal or intravenous injection at various doses. S1P levels in blood or tissues are measured by LC-MS to confirm target engagement. Efficacy endpoints depend on the disease model being studied. Pharmacokinetic studies may also be performed. |
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of PF-543 Citrate are not extensively documented. The compound has molecular weight 657.73 and molecular formula C33H3₉NO11S. It is soluble in DMSO (≥89.4 mg/mL), ethanol (≥28.33 mg/mL with gentle warming), and water (≥51.8 mg/mL with gentle warming). Purity is typically ≥98%. Storage at -20degC is recommended. Further detailed PK parameters would require dedicated studies.
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| Toxicity/Toxicokinetics |
Toxicological data for PF-543 Citrate are not well characterized in the public domain. As a research chemical, standard safety precautions should be observed. The compound is for laboratory use only and not intended for human therapeutic applications. SphK1 inhibitors as a class may have potential effects on immune function and vascular homeostasis. Comprehensive toxicity profiling would be required for therapeutic development.
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| References |
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| Additional Infomation |
PF-543 Citrate (CAS# 1415562-83-2) is a potent, selective, reversible, and sphingosine-competitive SPHK1 inhibitor. It has an IC₅0 of 2 nM and a Ki of 3.6 nM and is more than 100-fold selective for SphK1 over SphK2. It is used in sphingolipid metabolism research and is not approved for clinical use.
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| Molecular Formula |
C33H39NO11S
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|---|---|
| Molecular Weight |
657.727869272232
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| Exact Mass |
657.224
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| CAS # |
1415562-83-2
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| Related CAS # |
PF-543;1415562-82-1;PF-543 hydrochloride;1706522-79-3
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| PubChem CID |
71576669
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| Appearance |
White to yellow solid powder
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| LogP |
4.274
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
12
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| Rotatable Bond Count |
14
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| Heavy Atom Count |
46
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| Complexity |
906
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC1=CC(=CC(=C1)OCC2=CC=C(C=C2)CN3CCC[C@@H]3CO)CS(=O)(=O)C4=CC=CC=C4.C(C(=O)O)C(CC(=O)O)(C(=O)O)O
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| InChi Key |
PWXXWUWKNPXSGW-VQIWEWKSSA-N
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| InChi Code |
InChI=1S/C27H31NO4S.C6H8O7/c1-21-14-24(20-33(30,31)27-7-3-2-4-8-27)16-26(15-21)32-19-23-11-9-22(10-12-23)17-28-13-5-6-25(28)18-29;7-3(8)1-6(13,5(11)12)2-4(9)10/h2-4,7-12,14-16,25,29H,5-6,13,17-20H2,1H3;13H,1-2H2,(H,7,8)(H,9,10)(H,11,12)/t25-;/m1./s1
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| Chemical Name |
[(2R)-1-[[4-[[3-(benzenesulfonylmethyl)-5-methylphenoxy]methyl]phenyl]methyl]pyrrolidin-2-yl]methanol;2-hydroxypropane-1,2,3-tricarboxylic acid
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ≥ 100 mg/mL (~152.04 mM)
H2O : ~50 mg/mL (~76.02 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.80 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (3.80 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (3.80 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 100 mg/mL (152.04 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 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 | 0.1520 mL | 0.7602 mL | 1.5204 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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