| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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Purity: ≥98%
PF-543 (also called PF543; PF 543; Sphingosine Kinase 1 Inhibitor II) is a novel cell-permeable and sphingosine-competitive inhibitor of SphK1 with potential antitumor activity. It shows >100-fold selectivity for SphK1 over the SphK2 isoform and inhibits SphK1 with IC50s and Ki of 2.0 nM and 3.6 nM.
| Targets |
SphK1
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|---|---|---|---|
| ln Vitro |
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| ln Vivo |
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| Enzyme Assay |
The SphK enzyme assay, which uses a microfluidic capillary electrophoresis mobility-shift system to separate unreacted FITC-sphingosine substrate from FITC-S1P, is developed in a 384-well format. In summary, 1 μM FITC-sphingosine, 20 μM ATP, and 10 μM compound (with a final DMSO concentration of 2%), along with 3 nM SphK1–His6, are incubated for 1 hour in a 384-well Matrical MP-101-1-PP plate with a buffer that contains 100 mM Hepes (pH 7.4), 1 mM MgCl2, 0.01% Triton X-100, 10% glycerol, 100 μM sodium orthovanadate, and 1 mM DTT. The reaction mixtures (10 μL) are quenched by adding 20 μL of 30 mM EDTA and 0.15% Coating Reagent-3 in 100 mM Hepes. A small aliquot of each reaction, a few nanoliters, is then analyzed in the Caliper LabChip 3000 instrument at a downstream voltage of -1900 V, a sip time of 0.2 s, and a pressure of -1.5 psi (psi=6.9 kPa). The Caliper data are used to quantify the distinct peaks that appeared as phosphorylated fluorescent product and unphosphorylated fluorescent substrate.
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| Cell Assay |
In 1483 head and neck cancer cell cultures that expressed high levels of SphK1 and produced S1P at an exceptionally high rate, pretreatment with PF-543 for one hour reduced endogenous S1P levels by ten times while increasing sphingosine levels proportionately. Significant inhibition of SphK1 BY pf-543 was observed. Specific inhibition of SphK1, however, did not affect the survival and proliferation of 1483 cell cultures, even though the cellular S1P/sphingosine rate changed dramatically.
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| Animal Protocol |
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| References |
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| Additional Infomation |
[(2R)-1-[[4-[[3-(benzenesulfonylmethyl)-5-methylphenoxy]methyl]phenyl]methyl]-2-pyrrolidinyl]methanol is a sulfonamide.
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| Molecular Formula |
C27H31NO4S
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|---|---|---|
| Molecular Weight |
465.6
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| Exact Mass |
465.197
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| Elemental Analysis |
C, 69.65; H, 6.71; N, 3.01; O, 13.74; S, 6.89
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| CAS # |
1415562-82-1
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| Related CAS # |
PF-543 Citrate; 1415562-83-2; PF-543 hydrochloride; 1706522-79-3
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| PubChem CID |
66577038
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| Appearance |
White to off-white Waxy semisolid
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
666.0±55.0 °C at 760 mmHg
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| Flash Point |
356.6±31.5 °C
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| Vapour Pressure |
0.0±2.1 mmHg at 25°C
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| Index of Refraction |
1.610
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| LogP |
4.16
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
33
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| Complexity |
679
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC1=CC(OCC2=CC=C(CN3[C@@H](CO)CCC3)C=C2)=CC(CS(C4=CC=CC=C4)(=O)=O)=C1
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| InChi Key |
NPUXORBZRBIOMQ-RUZDIDTESA-N
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| InChi Code |
InChI=1S/C27H31NO4S/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/h2-4,7-12,14-16,25,29H,5-6,13,17-20H2,1H3/t25-/m1/s1
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| Chemical Name |
[(2R)-1-[[4-[[3-(benzenesulfonylmethyl)-5-methylphenoxy]methyl]phenyl]methyl]pyrrolidin-2-yl]methanol
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| Synonyms |
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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: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 5 mg/mL (10.74 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 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. Solubility in Formulation 2: ≥ 5 mg/mL (10.74 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 50.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1478 mL | 10.7388 mL | 21.4777 mL | |
| 5 mM | 0.4296 mL | 2.1478 mL | 4.2955 mL | |
| 10 mM | 0.2148 mL | 1.0739 mL | 2.1478 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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