PF-543 free base
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MedKoo CAT#: 556331

CAS#: 1415562-82-1 (free base)

Description: 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

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PF-543 free base
CAS# 1415562-82-1 (free base)
Instruction

Theoretical Analysis

MedKoo Cat#: 556331
Name: PF-543 free base
CAS#: 1415562-82-1 (free base)
Chemical Formula: C27H31NO4S
Exact Mass: 465.20
Molecular Weight: 465.608
Elemental Analysis: C, 69.65; H, 6.71; N, 3.01; O, 13.74; S, 6.89

Price and Availability

Size Price Availability Quantity
25mg USD 450 2 Weeks
50mg USD 750 2 Weeks
100mg USD 1250 2 Weeks
200mg USD 2250 2 Weeks
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Related CAS #: 1706522-79-3 (HCl)   1415562-82-1 (free base)   1415562-83-2 (citrate)    

Synonym: PF-543 free base; PF-543; PF543; PF 543;

IUPAC/Chemical Name: (R)-(1-(4-((3-methyl-5-((phenylsulfonyl)methyl)phenoxy)methyl)benzyl)pyrrolidin-2-yl)methanol

InChi Key: NPUXORBZRBIOMQ-RUZDIDTESA-N

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

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

Appearance: Waxy semisolid

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: To be determined

Shelf Life: >2 years if stored properly

Drug Formulation: To be determined

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:

Biological target:
In vitro activity:
In vivo activity:

Preparing Stock Solutions

The following data is based on the product molecular weight 465.61 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.

Recalculate based on batch purity %
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:
In vitro protocol:
In vivo protocol:

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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.