PF-543 HCl | CAS#1415562-82-1 | 1706522-79-3 | SK-1 inhibitor | 1415562-83-2

MedKoo Cat#: 406142 | Name: PF-543 HCl

Description:

WARNING: This product is for research use only, not for human or veterinary use.

PF-543 is a novel selective SK-1 inhibitor which inhibited SK-1 activity in a competitive manner with sphingosine. PF-543 inhibits SphK1 with a K(i) of 3.6 nM, is sphingosine-competitive and is more than 100-fold selective for SphK1 over the SphK2 isoform. PF-543 was 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. PF-543 is the most potent inhibitor of SphK1 described to date and it will be useful for dissecting specific roles of SphK1-driven S1P signalling.

Chemical Structure

PF-543 HCl

CAS#1706522-79-3 (HCl)

Theoretical Analysis

MedKoo Cat#: 406142

Name: PF-543 HCl

CAS#: 1706522-79-3 (HCl)

Chemical Formula: C27H32ClNO4S

Exact Mass:

Molecular Weight: 502.07

Elemental Analysis: C, 64.59; H, 6.42; Cl, 7.06; N, 2.79; O, 12.75; S, 6.39

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,350.00	Ready to ship
500mg	USD 2,650.00	Ready to Ship
1g	USD 4,450.00	Ready to Ship
2g	USD 6,450.00	2 Weeks

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Related CAS #

1706522-79-3 (HCl) 1415562-82-1 (free base) 1415562-83-2 (citrate)

Synonym

PF543; PF543; PF 543; PF-543 HCl; PF-543 citrate

IUPAC/Chemical Name

(R)-(1-(4-((3-methyl-5-((phenylsulfonyl)methyl)phenoxy)methyl)benzyl)pyrrolidin-2-yl)methanol hydrochoride

InChi Key

WNKWAZFYPZMDGJ-VQIWEWKSSA-N

InChi Code

InChI=1S/C27H31NO4S.ClH/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;1H/t25-;/m1./s1

SMILES Code

OC[C@@H]1N(CC2=CC=C(COC3=CC(CS(=O)(C4=CC=CC=C4)=O)=CC(C)=C3)C=C2)CCC1.[H]Cl

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#T23D05P30

QC Data

View QC data: current batch, Lot#T23D05P30

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

PF-543 HCl is a potent and selective SphK1 inhibitor (IC50 = 2 nM; Ki = 3.6 nM). PF-543 HCl exhibits >100-fold selectivity for Sphk1 over Sphk2. It exhibits >5,000 fold selectivity over S1P1-5 receptors and 48 protein and lipid kinases. PF-543 HCl attenuates proliferation and induces necrosis in human colorectal cancer cells in vitro. PF-543 HCl suppresses HCT-116 tumor xenograft growth in mice. It also reduces sickling, hemolysis and inflammation in a transgenic mouse model of sickle cell disease.

In vitro activity:

Treatment of head and neck squamous cell carcinoma cells with autophagy inhibitors and PF-543 increased the proportion of cells with necrosis and apoptosis, indicating that autophagy acts to promote cell survival. These results demonstrate that PF-543 induces apoptosis, necrosis, and autophagy in human head and neck squamous cell carcinoma cells, and that autophagy antagonizes either necrosis or apoptosis. Reference: Cell Death Discov. 2017 Aug 14;3:17047. https://pubmed.ncbi.nlm.nih.gov/29109864/

In vivo activity:

Administration of PF-543 in a mouse hypoxic model of pulmonary hypertension reduced right ventricular hypertrophy. The findings of this study with PF-543 suggest an important role for sphingosine kinase 1 in the development of hypertrophy in pulmonary arterial hypertension. Reference: Cell Signal. 2016 Aug;28(8):946-55. https://pubmed.ncbi.nlm.nih.gov/27063355/

	Solvent	mg/mL	mM
Solubility
	DMSO	50.2	100.00
	Water	5.0	10.00

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 502.07 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Kim SB, Limbu KR, Oh YS, Kim SL, Park SK, Baek DJ, Park EY. Novel Dimer Derivatives of PF-543 as Potential Antitumor Agents for the Treatment of Non-Small Cell Lung Cancer. Pharmaceutics. 2022 Sep 24;14(10):2035. doi: 10.3390/pharmaceutics14102035. PMID: 36297469; PMCID: PMC9611471. 2. Hamada M, Kameyama H, Iwai S, Yura Y. Induction of autophagy by sphingosine kinase 1 inhibitor PF-543 in head and neck squamous cell carcinoma cells. Cell Death Discov. 2017 Aug 14;3:17047. doi: 10.1038/cddiscovery.2017.47. PMID: 29109864; PMCID: PMC5554793. 3. MacRitchie N, Volpert G, Al Washih M, Watson DG, Futerman AH, Kennedy S, Pyne S, Pyne NJ. 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. doi: 10.1016/j.cellsig.2016.03.014. Epub 2016 Apr 6. PMID: 27063355; PMCID: PMC4913619. 4. Ju T, Gao D, Fang ZY. Targeting colorectal cancer cells by a novel sphingosine kinase 1 inhibitor PF-543. Biochem Biophys Res Commun. 2016 Feb 12;470(3):728-734. doi: 10.1016/j.bbrc.2016.01.053. Epub 2016 Jan 15. PMID: 26775841.

In vitro protocol:

In vivo protocol:

1. MacRitchie N, Volpert G, Al Washih M, Watson DG, Futerman AH, Kennedy S, Pyne S, Pyne NJ. 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. doi: 10.1016/j.cellsig.2016.03.014. Epub 2016 Apr 6. PMID: 27063355; PMCID: PMC4913619. 2. Ju T, Gao D, Fang ZY. Targeting colorectal cancer cells by a novel sphingosine kinase 1 inhibitor PF-543. Biochem Biophys Res Commun. 2016 Feb 12;470(3):728-734. doi: 10.1016/j.bbrc.2016.01.053. Epub 2016 Jan 15. PMID: 26775841.

1: Yi X, Tang X, Li T, Chen L, He H, Wu X, Xiang C, Cao M, Wang Z, Wang Y, Wang Y, Huang X. Therapeutic potential of the sphingosine kinase 1 inhibitor, PF-543. Biomed Pharmacother. 2023 Jul;163:114401. doi: 10.1016/j.biopha.2023.114401. Epub 2023 May 9. PMID: 37167721. 2: Sah RK, Anand S, Dar W, Jain R, Kumari G, Madan E, Saini M, Gupta A, Joshi N, Hada RS, Gupta N, Pati S, Singh S. Host-Erythrocytic Sphingosine-1-Phosphate Regulates Plasmodium Histone Deacetylase Activity and Exhibits Epigenetic Control over Cell Death and Differentiation. Microbiol Spectr. 2023 Feb 6;11(2):e0276622. doi: 10.1128/spectrum.02766-22. Epub ahead of print. PMID: 36744922; PMCID: PMC10100792. 3: Bonica J, Clarke CJ, Obeid LM, Luberto C, Hannun YA. Upregulation of sphingosine kinase 1 in response to doxorubicin generates an angiogenic response via stabilization of Snail. FASEB J. 2023 Mar;37(3):e22787. doi: 10.1096/fj.202201066R. PMID: 36723905; PMCID: PMC9979566. 4: Cong D, Yu Y, Meng Y, Qi X. Dexmedetomidine (Dex) exerts protective effects on rat neuronal cells injured by cerebral ischemia/reperfusion via regulating the Sphk1/S1P signaling pathway. J Stroke Cerebrovasc Dis. 2023 Jan;32(1):106896. doi: 10.1016/j.jstrokecerebrovasdis.2022.106896. Epub 2022 Nov 15. PMID: 36395661. 5: Lin Z, Li Y, Han X, Fu Z, Tian Z, Li C. Targeting SPHK1/PBX1 Axis Induced Cell Cycle Arrest in Non-Small Cell Lung Cancer. Int J Mol Sci. 2022 Oct 22;23(21):12741. doi: 10.3390/ijms232112741. PMID: 36361531; PMCID: PMC9657307. 6: Kim SB, Limbu KR, Oh YS, Kim SL, Park SK, Baek DJ, Park EY. Novel Dimer Derivatives of PF-543 as Potential Antitumor Agents for the Treatment of Non- Small Cell Lung Cancer. Pharmaceutics. 2022 Sep 24;14(10):2035. doi: 10.3390/pharmaceutics14102035. PMID: 36297469; PMCID: PMC9611471. 7: Kim SB, Oh YS, Kim KJ, Cho SW, Park SK, Baek DJ, Park EY. Synthesis of PP2A-Activating PF-543 Derivatives and Investigation of Their Inhibitory Effects on Pancreatic Cancer Cells. Molecules. 2022 May 23;27(10):3346. doi: 10.3390/molecules27103346. PMID: 35630821; PMCID: PMC9145885. 8: Zhang S, Chen X, Wu C, Xu H, Xie X, Feng M, Hu S, Bai H, Gao F, Tong L, Ding J, Liu H, Xie Z, Wang J. Novel Sphingosine Kinase 1 Inhibitor Suppresses Growth of Solid Tumor and Inhibits the Lung Metastasis of Triple-Negative Breast Cancer. J Med Chem. 2022 Jun 9;65(11):7697-7716. doi: 10.1021/acs.jmedchem.2c00040. Epub 2022 Apr 19. PMID: 35439002. 9: Fakhr Y, Koshti S, Habibyan YB, Webster K, Hemmings DG. Tumor Necrosis Factor-α Induces a Preeclamptic-like Phenotype in Placental Villi via Sphingosine Kinase 1 Activation. Int J Mol Sci. 2022 Mar 29;23(7):3750. doi: 10.3390/ijms23073750. PMID: 35409108; PMCID: PMC8998215. 10: Thomas JM, Sudhadevi T, Basa P, Ha AW, Natarajan V, Harijith A. The Role of Sphingolipid Signaling in Oxidative Lung Injury and Pathogenesis of Bronchopulmonary Dysplasia. Int J Mol Sci. 2022 Jan 23;23(3):1254. doi: 10.3390/ijms23031254. PMID: 35163176; PMCID: PMC8835774. 11: Shrestha J, Kim SW, Kim SB, Oh YS, Ki SH, Lee T, Kim SB, Park T, Baek DJ, Park EY. Determining the Anticancer Activity of Sphingosine Kinase Inhibitors Containing Heteroatoms in Their Tail Structure. Pharmaceutics. 2022 Jan 10;14(1):157. doi: 10.3390/pharmaceutics14010157. PMID: 35057052; PMCID: PMC8779255. 12: Brew T, Bougen-Zhukov N, Mitchell W, Decourtye L, Schulpen E, Nouri Y, Godwin T, Guilford P. Loss of E-Cadherin Leads to Druggable Vulnerabilities in Sphingolipid Metabolism and Vesicle Trafficking. Cancers (Basel). 2021 Dec 26;14(1):102. doi: 10.3390/cancers14010102. PMID: 35008266; PMCID: PMC8749886. 13: Molinar-Inglis O, Birch CA, Nicholas D, Orduña-Castillo L, Cisneros-Aguirre M, Patwardhan A, Chen B, Grimsey NJ, Coronel LJ, Lin H, Gomez Menzies PK, Lawson MA, Patel HH, Trejo J. aPC/PAR1 confers endothelial anti-apoptotic activity via a discrete, β-arrestin-2-mediated SphK1-S1PR1-Akt signaling axis. Proc Natl Acad Sci U S A. 2021 Dec 7;118(49):e2106623118. doi: 10.1073/pnas.2106623118. PMID: 34873055; PMCID: PMC8670512. 14: Lin HM, Mak B, Yeung N, Huynh K, Meikle TG, Mellett NA, Kwan EM, Fettke H, Tran B, Davis ID, Mahon KL, Zhang A, Stockler MR, Briscoe K, Marx G, Crumbaker M, Stricker PD, Du P, Yu J, Jia S, Scheinberg T, Fitzpatrick M, Bonnitcha P, Sullivan DR, Joshua AM, Azad AA, Butler LM, Meikle PJ, Horvath LG. Overcoming enzalutamide resistance in metastatic prostate cancer by targeting sphingosine kinase. EBioMedicine. 2021 Oct;72:103625. doi: 10.1016/j.ebiom.2021.103625. Epub 2021 Oct 14. PMID: 34656931; PMCID: PMC8526762. 15: Shamshiddinova M, Gulyamov S, Kim HJ, Jung SH, Baek DJ, Lee YM. A Dansyl- Modified Sphingosine Kinase Inhibitor DPF-543 Enhanced De Novo Ceramide Generation. Int J Mol Sci. 2021 Aug 25;22(17):9190. doi: 10.3390/ijms22179190. PMID: 34502095; PMCID: PMC8431253. 16: Deng R, Bu Y, Li F, Wu H, Wang Y, Wei W. The interplay between fibroblast- like synovial and vascular endothelial cells leads to angiogenesis via the sphingosine-1-phosphate-induced RhoA-F-Actin and Ras-Erk1/2 pathways and the intervention of geniposide. Phytother Res. 2021 Sep;35(9):5305-5317. doi: 10.1002/ptr.7211. Epub 2021 Jul 29. PMID: 34327764. 17: León Y, Magariños M, Varela-Nieto I. Ceramide Kinase Inhibition Blocks IGF-1-Mediated Survival of Otic Neurosensory Progenitors by Impairing AKT Phosphorylation. Front Cell Dev Biol. 2021 Jun 4;9:678760. doi: 10.3389/fcell.2021.678760. PMID: 34179008; PMCID: PMC8220815. 18: Chen L, Li L, Song Y, Lv T. Blocking SphK1/S1P/S1PR1 Signaling Pathway Alleviates Lung Injury Caused by Sepsis in Acute Ethanol Intoxication Mice. Inflammation. 2021 Dec;44(6):2170-2179. doi: 10.1007/s10753-021-01490-3. Epub 2021 Jun 9. PMID: 34109517; PMCID: PMC8189277. 19: Wang C, Xu T, Lachance BB, Zhong X, Shen G, Xu T, Tang C, Jia X. Critical roles of sphingosine kinase 1 in the regulation of neuroinflammation and neuronal injury after spinal cord injury. J Neuroinflammation. 2021 Feb 18;18(1):50. doi: 10.1186/s12974-021-02092-4. PMID: 33602274; PMCID: PMC7893778. 20: Li H, Sibley CD, Kharel Y, Huang T, Brown AM, Wonilowicz LG, Bevan DR, Lynch KR, Santos WL. Lipophilic tail modifications of 2-(hydroxymethyl)pyrrolidine scaffold reveal dual sphingosine kinase 1 and 2 inhibitors. Bioorg Med Chem. 2021 Jan 15;30:115941. doi: 10.1016/j.bmc.2020.115941. Epub 2020 Dec 13. PMID: 33385956; PMCID: PMC8862572.