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Chemical Structure| 1706522-79-3 Chemical Structure| 1706522-79-3

Structure of PF-543 HCl
CAS No.: 1706522-79-3

Chemical Structure| 1706522-79-3

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PF-543 HCl is a cell-permeant inhibitor of SphK1 with a Ki of 3.6 nM, PF-543 is sphingosine-competitive and is more than 100-fold selective for SphK1 over the SphK2 isoform.

Synonyms: Sphingosine Kinase 1 Inhibitor II hydrochloride; PF-543 (hydrochloride); PF-543 hydrochloride

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Product Details of PF-543 HCl

CAS No. :1706522-79-3
Formula : C27H32ClNO4S
M.W : 502.07
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
Synonyms :
Sphingosine Kinase 1 Inhibitor II hydrochloride; PF-543 (hydrochloride); PF-543 hydrochloride
MDL No. :MFCD28411614
InChI Key :WNKWAZFYPZMDGJ-VQIWEWKSSA-N
Pubchem ID :121230770

Safety of PF-543 HCl

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
HAPI cells 10 nM and 100 nM 12 hours PF543 pretreatment attenuated LPS-induced M1 microglia polarization and proinflammatory cytokine production. J Neuroinflammation. 2021 Feb 18;18(1):50.
PC12 cells 0.1 µM 12 hours PF543 pretreatment significantly attenuated neuronal apoptosis induced by M1 microglia. J Neuroinflammation. 2021 Feb 18;18(1):50.
Huh7 HCC cells 5 µM 16 hours To evaluate the effects of PF-543 on Huh7 HCC cells, results showed that PF-543 significantly reduced S1P levels but did not affect cell viability, cell death, or clonogenicity J Transl Med. 2024 Jan 10;22(1):43.
Human umbilical vein endothelial cells (HUVECs) 5 µM 16 hours To evaluate the effects of PF-543 on endothelial cell angiogenesis, results showed that PF-543 significantly inhibited tube formation, migration, and sprouting but did not affect cell viability or cell death J Transl Med. 2024 Jan 10;22(1):43.
Human head and neck SCC cell lines 1, 5, 10, 25, or 50 µM 24, 48, and 72 hours To assess cell viability and types of cell death induced by PF-543. Cell Death Discov. 2017 Aug 14;3:17047.
Sickle cells up to 50 µM PF-543 inhibited SPHK1 activity and reduced sickle cell formation under hypoxic conditions without causing hemolysis J Clin Invest. 2014 Jun;124(6):2750-61.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
SCD Tg mice Sickle cell disease model Subcutaneous injection 0.93 mg/kg/day Once daily for 28 days PF-543 treatment significantly reduced SPHK1 activity, S1P levels, and the percentage of sickle cells in SCD mice, and also reduced hemolysis and inflammation J Clin Invest. 2014 Jun;124(6):2750-61.
Sprague-Dawley rats Spinal cord injury model Intraperitoneal injection 10 mg/kg Daily until sacrifice PF543 attenuated inflammation and neuronal damage after spinal cord injury, leading to improved functional recovery. J Neuroinflammation. 2021 Feb 18;18(1):50.
Mice Ang II-infused hypertensive mice Injection 10 mg/kg Every 2 days PF543 mitigated cardiac hypertrophy and improved endothelial function without affecting blood pressure. Hypertension. 2020 Feb;75(2):383-392
SCD Tg mice Diethylnitrosamine (DEN)-induced primary liver cancer model Intraperitoneal injection 25 mg/kg Every other day for 12 weeks To evaluate the inhibitory effects of PF-543 on DEN-induced primary liver cancer, results showed that PF-543 significantly inhibited SphK1 activity, reduced tumor number and size, and decreased tumor angiogenesis J Transl Med. 2024 Jan 10;22(1):43.

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.99mL

0.40mL

0.20mL

9.96mL

1.99mL

1.00mL

19.92mL

3.98mL

1.99mL

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