PF-543SphK1 inhibitor,cell-permeate,potent and selective CAS# 1415562-82-1 |
- SKI II
Catalog No.:BCC5029
CAS No.:312636-16-1
Quality Control & MSDS
3D structure
Package In Stock
Number of papers citing our products
| Cas No. | 1415562-82-1 | SDF | Download SDF |
| PubChem ID | 66577038 | Appearance | Powder |
| Formula | C27H31NO4S | M.Wt | 465.6 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | Soluble in DMSO > 10 mM | ||
| Chemical Name | [(2R)-1-[[4-[[3-(benzenesulfonylmethyl)-5-methylphenoxy]methyl]phenyl]methyl]pyrrolidin-2-yl]methanol | ||
| SMILES | CC1=CC(=CC(=C1)OCC2=CC=C(C=C2)CN3CCCC3CO)CS(=O)(=O)C4=CC=CC=C4 | ||
| Standard InChIKey | NPUXORBZRBIOMQ-RUZDIDTESA-N | ||
| Standard InChI | 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 | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
||
| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
||
| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | PF-543 is a novel cell-permeable inhibitor of SphK1 with Ki value of 3.6 nM. | |||||
| Targets | SphK1 | |||||
| IC50 | 3.6 nM (Ki) | |||||
PF-543 Dilution Calculator
PF-543 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 2.1478 mL | 10.7388 mL | 21.4777 mL | 42.9553 mL | 53.6942 mL |
| 5 mM | 0.4296 mL | 2.1478 mL | 4.2955 mL | 8.5911 mL | 10.7388 mL |
| 10 mM | 0.2148 mL | 1.0739 mL | 2.1478 mL | 4.2955 mL | 5.3694 mL |
| 50 mM | 0.043 mL | 0.2148 mL | 0.4296 mL | 0.8591 mL | 1.0739 mL |
| 100 mM | 0.0215 mL | 0.1074 mL | 0.2148 mL | 0.4296 mL | 0.5369 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
Calcutta University
University of Minnesota
University of Maryland School of Medicine
University of Illinois at Chicago
The Ohio State University
University of Zurich
Harvard University
Colorado State University
Auburn University
Yale University
Worcester Polytechnic Institute
Washington State University
Stanford University
University of Leipzig
Universidade da Beira Interior
The Institute of Cancer Research
Heidelberg University
University of Amsterdam
University of Auckland
TsingHua University
The University of Michigan
Miami University
DRURY University
Jilin University
Fudan University
Wuhan University
Sun Yat-sen University
Universite de Paris
Deemed University
Auckland University
The University of Tokyo
Korea University
PF-543 is a novel and cell-permeant inhibitor of Sphingosine kinase (SphK1) with IC50 value of 3.6 nM [1],
SphK1 is a kinase that phosphorylates sphingosine to sphingosine-1-phosphate (SIP). SphK1 is normally a cytosolic protein but can be recruited to the membrane to conduct its activity. It is the major source of production of S1P which promotes cell growth, survival and migration, and also regulate lymphocyte trafficking.
Biochemical study has identified that SphK1 was a sphingosine-competitive inhibitor but not ATP-competitive [1]. In 1483 head and neck carcinoma cell cultures expressing high levels of SphK1 and with an unusually high rate of S1P production, pretreatment of PF-543 for 1 hr decreased the level of endogenous S1P by 10-fold with a proportional increase in the level of sphingosine. It indicated a significant inhibition of SphK1 BY pf-543. However, specific inhibition of SphK1 had no effect on the proliferation and survival of 1483 cell cultures, despite a dramatic change in the cellular S1P/sphingosine rate [1].
The inhibitory activity of PF-543 was also examined ex vivo in human whole blood. Human whole blood with high SphK1 activity was prepared, which was able to quickly convert C17-sphingosine to C17-S1P. PF-543 treatment showed that PF-543 was a potent inhibitor of SphK1, capable of blocking >90% C17-S1P formation [1].
Reference:
[1] Schnute M E et al. , Modulation of cellular S1P levels with a novel, potent and specific inhibitor of sphingosine kinase-1. Biochem J. 2012, 444(1): 79-88.
- Crizotinib hydrochloride
Catalog No.:BCC5306
CAS No.:1415560-69-8
- GSK256066 2,2,2-trifluoroacetic acid
Catalog No.:BCC1605
CAS No.:1415560-64-3
- CDK9 inhibitor
Catalog No.:BCC1465
CAS No.:1415559-43-1
- MK-8245 Trifluoroacetate
Catalog No.:BCC1769
CAS No.:1415559-41-9
- LY 231617
Catalog No.:BCC7005
CAS No.:141545-89-3
- Pelandjauic acid
Catalog No.:BCN3752
CAS No.:141545-69-9
- 5S rRNA modificator
Catalog No.:BCC5442
CAS No.:1415238-77-5
- Levosimendan
Catalog No.:BCC4793
CAS No.:141505-33-1
- Aloin A
Catalog No.:BCN1042
CAS No.:1415-73-2
- Rauvoyunine B
Catalog No.:BCN6995
CAS No.:1414883-82-1
- Rauvoyunine A
Catalog No.:BCN7002
CAS No.:1414883-81-0
- Guajadial B
Catalog No.:BCN3972
CAS No.:1414455-03-0
- PF-543 Citrate
Catalog No.:BCC1855
CAS No.:1415562-83-2
- ST-836 hydrochloride
Catalog No.:BCC1969
CAS No.:1415564-68-9
- Angustin A
Catalog No.:BCN7651
CAS No.:1415795-50-4
- Angustin B
Catalog No.:BCN7652
CAS No.:1415795-51-5
- UNC1215
Catalog No.:BCC2023
CAS No.:1415800-43-9
- JW 642
Catalog No.:BCC6324
CAS No.:1416133-89-5
- Beta-D-glucopyranosyl oleanolate
Catalog No.:BCN6530
CAS No.:14162-53-9
- Dronedarone HCl
Catalog No.:BCC4777
CAS No.:141625-93-6
- (±)-BI-D
Catalog No.:BCC5537
CAS No.:1416258-16-6
- Dronedarone
Catalog No.:BCN2176
CAS No.:141626-36-0
- CU CPT 22
Catalog No.:BCC6320
CAS No.:1416324-85-0
- GR 94800
Catalog No.:BCC5799
CAS No.:141636-65-9
Targeting colorectal cancer cells by a novel sphingosine kinase 1 inhibitor PF-543.[Pubmed:26775841]
Biochem Biophys Res Commun. 2016 Feb 12;470(3):728-734.
In this study, we showed that PF-543, a novel sphingosine kinase 1 (SphK1) inhibitor, exerted potent anti-proliferative and cytotoxic effects against a panel of established (HCT-116, HT-29 and DLD-1) and primary human colorectal cancer (CRC) cells. Its sensitivity was negatively associated with SphK1 expression level in the CRC cells. Surprisingly, PF-543 mainly induced programmed necrosis, but not apoptosis, in the CRC cells. CRC cell necrotic death was detected by lactate dehydrogenase (LDH) release, mitochondrial membrane potential (MMP) collapse and mitochondrial P53-cyclophilin-D (Cyp-D) complexation. Correspondingly, the necrosis inhibitor necrostatin-1 largely attenuated PF-543-induced cytotoxicity against CRC cells. Meanwhile, the Cyp-D inhibitors (sanglifehrin A and cyclosporin A), or shRNA-mediated knockdown of Cyp-D, remarkably alleviated PF-543-induced CRC cell necrotic death. Reversely, over-expression of wild-type Cyp-D in HCT-116 cells significantly increased PF-543's sensitivity. In vivo, PF-543 intravenous injection significantly suppressed HCT-116 xenograft growth in severe combined immunodeficient (SCID) mice, whiling remarkably improving the mice survival. The in vivo activity by PF-543 was largely attenuated when combined with the Cyp-D inhibitor cyclosporin A. Collectively, our results demonstrate that PF-543 exerts potent anti-CRC activity in vitro and in vivo. Mitochondrial programmed necrosis pathway is likely the key mechanism responsible for PF-543's actions in CRC cells.
Crystal Structure of Sphingosine Kinase 1 with PF-543.[Pubmed:25516793]
ACS Med Chem Lett. 2014 Oct 27;5(12):1329-33.
The most potent inhibitor of Sphingosine Kinase 1 (SPHK1) so far identified is PF-543. The crystal structure of SPHK1 in complex with inhibitor PF-543 to 1.8 A resolution reveals the inhibitor bound in a bent conformation analogous to that expected of a bound sphingosine substrate but with a rotated head group. The structural data presented will aid in the design of SPHK1 and SPHK2 inhibitors with improved properties.
Effect of the sphingosine kinase 1 selective inhibitor, PF-543 on arterial and cardiac remodelling in a hypoxic model of pulmonary arterial hypertension.[Pubmed:27063355]
Cell Signal. 2016 Aug;28(8):946-55.
Recent studies have demonstrated that the expression of sphingosine kinase 1, the enzyme that catalyses formation of the bioactive lipid, sphingosine 1-phosphate, is increased in lungs from patients with pulmonary arterial hypertension. In addition, Sk1(-/-) mice are protected from hypoxic-induced pulmonary arterial hypertension. Therefore, we assessed the effect of the sphingosine kinase 1 selective inhibitor, PF-543 and a sphingosine kinase 1/ceramide synthase inhibitor, RB-005 on pulmonary and cardiac remodelling in a mouse hypoxic model of pulmonary arterial hypertension. Administration of the potent sphingosine kinase 1 inhibitor, PF-543 in a mouse hypoxic model of pulmonary hypertension had no effect on vascular remodelling but reduced right ventricular hypertrophy. The latter was associated with a significant reduction in cardiomyocyte death. 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 (erythroid-derived 2)-like 2 (Nrf-2). In contrast, RB-005 lacked effects on right ventricular hypertrophy, suggesting that sphingosine kinase 1 inhibition might be nullified by concurrent inhibition of ceramide synthase. Therefore, our findings with PF-543 suggest an important role for sphingosine kinase 1 in the development of hypertrophy in pulmonary arterial hypertension.
