|
|
| | PF-543 HCl Basic information |
| Product Name: | PF-543 HCl | | Synonyms: | WNKWAZFYPZMDGJ-VQIWEWKSSA-N;(2R)-1-[[(4-[[3-Methyl-5-[(phenylsulfonyl)methyl]phenoxy]methyl]phenyl]methyl]-2-pyrrolidinemethanol hydrochloride;PF 543 HCl;PF-543 Hydrochloride
DISCONTINUED;Nrf-2,PF543 hydrochloride,anti-cancer,sphingosine-competitive,S1P,Sphingosine Kinase 1 Inhibitor II,Apoptosis,inhibit,PF 543,Lysophospholipid Receptor,PAH,necrosis,SphK,Inhibitor,Autophagy,PF543,PF 543 hydrochloride,caspase-3/7,SK1,Sphingosine kinase,LPL Receptor,anti-inflammatory;PF-543 hydrochloride, 10 mM in DMSO;PF-543 hydrochloride ，S7177 | | CAS: | 1706522-79-3 | | MF: | C27H32ClNO4S | | MW: | 502.07 | | EINECS: | | | Product Categories: | | | Mol File: | 1706522-79-3.mol |  |
| | PF-543 HCl Chemical Properties |
| Melting point | 156-158oC (dec.) | | storage temp. | under inert gas (nitrogen or Argon) at 2-8°C | | solubility | DMSO, Methanol | | form | Solid | | color | Beige |
| | PF-543 HCl Usage And Synthesis |
| Uses | (2R)-1-[[4-[[3-Methyl-5-[(phenylsulfonyl)methyl]phenoxy]methyl]phenyl]methyl]-2-pyrrolidinemethanol, is a novel Sphingonise Kinas 1 (SphK1, SK1) inhibitor. | | Enzyme inhibitor | This potent SphK1 inhibitor (FWHCl-Salt = 502.07 g/mol; CAS 1706522-79- 3; Solubility: 10 mM in H2O, with gentle warming; 100 mM in DMSO), also named (2R)-1-[[(4-[[3-methyl-5-[(phenylsulfonyl)methyl]phenoxy] methyl]phenyl]methyl]-2-pyrrolidinemethanol hydrochloride, selectively targets sphingosine kinase 1 (IC50 = 2 nM; Ki = 3.6 nM). The latter phosphorylates sphingosine to form sphingosine-1-phosphate (S1P), a lipid messenger with both intracellular functions (regulating cell proliferation and survival) and extracellular functions (as a ligand for EDG1, or sphingosine-1-phosphate receptor 1). PF-543 also exhibits >100-fold selectivity for Sphk1 over Sphk2 as well as >5000 fold selectivity over S1P1-5 receptors and 48 protein and lipid kinases. P 543 attenuates proliferation and induces necrosis in human colorectal cancer cells in vitro. It also suppresses human colorectal cancer cell line HCT-116 as a tumor xenograft growth in mice | | in vivo | PF-543 (1 mg/kg; intraperitoneal injection; every second day; for 21 days; female C57BL/6 J mice) treatment has no effect on vascular remodelling but reduces right ventricular hypertrophy. The protection involves a reduction in the expression of p53 and an increase in the expression of anti-oxidant nuclear factor Nrf-2[2].
Mice are initially dosed (ip) with 10 mg/kg or 30 mg/kg of PF-543 for 24 h and the T1/2 is 1.2 h in blood samples. Administration of 10 mg/kg PF-543 for 24 h to mice induces a decrease in SK1 expression in pulmonary vessels[2]. | Animal Model: | Female C57BL/6 J mice (7-12 week-old) with hypoxic-induced pulmonary arterial hypertension[2] | | Dosage: | 1 mg/kg | | Administration: | Intraperitoneal injection; every second day; for 21 days | | Result: | Reduced right ventricular hypertrophy. The protection involves a reduction in the expression of p53 (that promotes cardiomyocyte death) and an increase in the expression of anti-oxidant nuclear factor Nrf-2.
|
| | IC 50 | SphK1 | | storage | Desiccate at RT |
| | PF-543 HCl Preparation Products And Raw materials |
|