PF-543 hydrochloride

製品コードS7177 バッチS717702

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C27H32ClNO4S
分子量 502.07 CAS No. 1706522-79-3
Solubility (25°C)* 体外 DMSO 100 mg/mL (199.17 mM)
Ethanol 100 mg/mL (199.17 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 PF-543 hydrochloride, a novel sphingosine-competitive inhibitor of SphK1, inhibits SphK1 with IC50 and Ki of 2.0 nM and 3.6 nM, exhibits >100-fold selectivity over the SphK2 isoform. PF-543 hydrochloride induces apoptosis, necrosis, and autophagy.
in vitro

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]
in vivo

PF-543, a potent sphingosine kinase 1 inhibitor, reduced dysfunctional hypertrophy, associated with protection against cardiomyocyte apoptosis.
特徴 The most potent inhibitor of SphK1 described to date.

プロトコル(参考用のみ)

キナーゼアッセイ 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.
細胞アッセイ 細胞株 1483, A549, LN229, Jurkat, U937, MCF-7
濃度 ~1 μM
反応時間 7 days
実験の流れ

CellTiter-Glo Assay
動物実験 動物モデル C57BL/6 mice
投薬量 1 mg/kg
投与方法 i.p.

カスタマーフィードバック

Data from [Data independently produced by , , Int J Biochem Cell Biol, 2017, 90:17-28]

Data from [Data independently produced by , , Biochem Biophys Res Commun, 2016, 470(3):728-34.]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Targeting the SphK1/S1P/PFKFB3 axis suppresses hepatocellular carcinoma progression by disrupting glycolytic energy supply that drives tumor angiogenesis [ J Transl Med, 2024, 22(1):43] PubMed: 38200582
Induction of Inflammation Disrupts the Negative Interplay between STING and S1P Axis That Is Observed during Physiological Conditions in the Lung [ Int J Mol Sci, 2023, 24(9)8303] PubMed: 37176007
Comprehensive metabolomics expands precision medicine for triple-negative breast cancer [ Cell Res, 2022, 10.1038/s41422-022-00614-0] PubMed: 35105939
Sphingosine kinase 1 promotes tumor immune evasion by regulating the MTA3-PD-L1 axis [ Cell Mol Immunol, 2022, 19(10):1153-1167] PubMed: 36050478
Targeting sphingosine kinase 1/2 by a novel dual inhibitor SKI-349 suppresses non-small cell lung cancer cell growth [ Cell Death Dis, 2022, 13(7):602] PubMed: 35831279
The anti-osteosarcoma cell activity by the sphingosine kinase 1 inhibitor SKI-V [ Cell Death Discov, 2022, 8(1):48] PubMed: 35115496
S1P-Induced TNF-α and IL-6 Release from PBMCs Exacerbates Lung Cancer-Associated Inflammation [ Cells, 2022, 11-162524] PubMed: 36010601
Regulatory Role of Sphingosine-1-Phosphate and C16:0 Ceramide, in Immunogenic Cell Death of Colon Cancer Cells Induced by Bak/Bax-Activation [ Cancers (Basel), 2022, 14(21)5182] PubMed: 36358599
Design, Synthesis and Biological Activity Testing of Library of Sphk1 Inhibitors [ Molecules, 2022, 27(6)2020] PubMed: 35335379
Upregulated flotillins and sphingosine kinase 2 derail AXL vesicular traffic to promote epithelial-mesenchymal transition [ J Cell Sci, 2022, 135(7)jcs259178] PubMed: 35394045

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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