PF-543 hydrochloride

製品コードS7177 バッチS717703

印刷

化学情報

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

体内（毎回新しく調製した物を用意してください）

Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	5.000mg/ml (9.96mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	0.800mg/ml (1.59mM)	Taking the 1 mL working solution as an example, add 50 μL of 16 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

* <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 K_i 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, this compound decreases the level of endogenous S1P 10-fold with a proportional increase in the level of sphingosine. It binds SphK1 reversibly (k _off t1/2=8.5 min) and with high affinity and the binding constant (K_d) is 5 nM. This chemical 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. It 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 hydrochloride, 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
キナーゼアッセイ	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 this 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.

参考

https://pubmed.ncbi.nlm.nih.gov/22397330/
https://pubmed.ncbi.nlm.nih.gov/27063355/

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：

SPHK1 enhances olaparib resistance in ovarian cancer through the NFκB/NRF2/ferroptosis pathway [ Cell Death Discov, 2025, 11(1):29]	PubMed: 39875359
Elevated Sphingosine Levels Suppress Profibrotic TGF-β Signaling via the PKC/miR-21/SMAD7 Axis in Sphingosine Kinase 2-Deficient Renal Fibroblasts and Unilateral Ureteral Obstruction-Induced Kidney Fibrosis [ FASEB J, 2025, 39(12):e70768]	PubMed: 40558859
Elevated Sphingosine Levels Suppress Profibrotic TGF-β Signaling via the PKC/miR-21/SMAD7 Axis in Sphingosine Kinase 2-Deficient Renal Fibroblasts and Unilateral Ureteral Obstruction-Induced Kidney Fibrosis [ FASEB J, 2025, 39(12):e70768]	PubMed: 40558859
Molecular subtyping of renal clear cell carcinoma based on prognostic RASSF family genes and validation of C1QL1 as a key prognostic marker [ Sci Rep, 2025, 15(1):9786]	PubMed: 40118977
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
Cannabinoid-Induced Immunogenic Cell Death of Colorectal Cancer Cells Through De Novo Synthesis of Ceramide Is Partially Mediated by CB2 Receptor [ Cancers (Basel), 2024, 16(23)3973]	PubMed: 39682160
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
Sphingosine kinase 1 promotes tumor immune evasion by regulating the MTA3-PD-L1 axis [ Cell Mol Immunol, 2022, 19(10):1153-1167]	PubMed: 36050478

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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