PF-543 (Citrate)

Modify Date: 2024-01-02 17:11:43

PF-543 (Citrate) structure	Common Name	PF-543 (Citrate)
	CAS Number	1415562-83-2	Molecular Weight	657.72800
	Density	N/A	Boiling Point	N/A
	Molecular Formula	C₃₃H₃₉NO₁₁S	Melting Point	N/A
	MSDS	N/A	Flash Point	N/A

Use of PF-543 (Citrate)

PF-543 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.

Name	[(2R)-1-[[4-[[3-(benzenesulfonylmethyl)-5-methylphenoxy]methyl]phenyl]methyl]pyrrolidin-2-yl]methanol,2-hydroxypropane-1,2,3-tricarboxylic acid
Synonym	More Synonyms

Description	PF-543 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.
Related Catalog	Signaling Pathways >> Immunology/Inflammation >> SPHK Research Areas >> Cancer
Target	Ki: 3.6 nM (SPHK1)[1]
In Vitro	PF-543 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].
In Vivo	Administration of the potent sphingosine kinase 1 inhibitor, PF-543 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].
Cell Assay	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 Admin	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. [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.

Molecular Formula	C₃₃H₃₉NO₁₁S
Molecular Weight	657.72800
Exact Mass	657.22400
PSA	207.35000
LogP	4.27480
Storage condition	2-8℃

CS-1072

PF-543 Citrate||PF 543 Citrate

PF 543 Citrate

PF-543 (Citrate)