N,N-DimethylsphingosineSphingosine kinase inhibitor CAS# 119567-63-4 |
- SU14813
Catalog No.:BCC1971
CAS No.:627908-92-3
Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
Cas No. | 119567-63-4 | SDF | Download SDF |
PubChem ID | 5282309 | Appearance | Powder |
Formula | C20H41NO2 | M.Wt | 327.55 |
Type of Compound | N/A | Storage | Desiccate at -20°C |
Solubility | Soluble to 30 mM in DMSO | ||
Chemical Name | (E,2S,3R)-2-(dimethylamino)octadec-4-ene-1,3-diol | ||
SMILES | CCCCCCCCCCCCCC=CC(C(CO)N(C)C)O | ||
Standard InChIKey | YRXOQXUDKDCXME-YIVRLKKSSA-N | ||
Standard InChI | InChI=1S/C20H41NO2/c1-4-5-6-7-8-9-10-11-12-13-14-15-16-17-20(23)19(18-22)21(2)3/h16-17,19-20,22-23H,4-15,18H2,1-3H3/b17-16+/t19-,20+/m0/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 | Competitive sphingosine kinase (SphK) inhibitor. Exhibits inhibitory activity in platelets and in cytosolic extracts from U937, Swiss 3T3 and PC12 cells. Selectively inhibits sphingosine phosphorylation; does not inhibit N-acylation, and displays no inhibitory effect on protein kinase C at concentrations that inhibit SphK. Increases the release of IL-1β and MCP-1 in cultured astrocytes; thought to mediate mechanical allodynia via this mechanism. |
N,N-Dimethylsphingosine Dilution Calculator
N,N-Dimethylsphingosine Molarity Calculator
1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
1 mM | 3.053 mL | 15.2648 mL | 30.5297 mL | 61.0594 mL | 76.3242 mL |
5 mM | 0.6106 mL | 3.053 mL | 6.1059 mL | 12.2119 mL | 15.2648 mL |
10 mM | 0.3053 mL | 1.5265 mL | 3.053 mL | 6.1059 mL | 7.6324 mL |
50 mM | 0.0611 mL | 0.3053 mL | 0.6106 mL | 1.2212 mL | 1.5265 mL |
100 mM | 0.0305 mL | 0.1526 mL | 0.3053 mL | 0.6106 mL | 0.7632 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
- Othonnine
Catalog No.:BCN2061
CAS No.:119565-25-2
- Ceanothic acid acetate
Catalog No.:BCN6083
CAS No.:119533-63-0
- Ethyllucidone
Catalog No.:BCN6082
CAS No.:1195233-59-0
- Meropenem trihydrate
Catalog No.:BCC4226
CAS No.:119478-56-7
- Fruquintinib(HMPL-013)
Catalog No.:BCC6415
CAS No.:1194506-26-7
- Eliprodil
Catalog No.:BCC7280
CAS No.:119431-25-3
- Loureirin B
Catalog No.:BCN5021
CAS No.:119425-90-0
- Loureirin A
Catalog No.:BCN3671
CAS No.:119425-89-7
- Galanin (1-30) (human)
Catalog No.:BCC6961
CAS No.:119418-04-1
- Licoricesaponin E2
Catalog No.:BCN7894
CAS No.:119417-96-8
- Topotecan hydrochloride
Catalog No.:BCN2604
CAS No.:119413-54-6
- LY2811376
Catalog No.:BCC2102
CAS No.:1194044-20-6
- 11-Hydroxygelsenicine
Catalog No.:BCN4761
CAS No.:1195760-68-9
- Dabrafenib (GSK2118436)
Catalog No.:BCC4393
CAS No.:1195765-45-7
- Dabrafenib Mesylate (GSK-2118436)
Catalog No.:BCC1513
CAS No.:1195768-06-9
- 7-Ethyl-10-Hydroxy-Camptothecin
Catalog No.:BCN8386
CAS No.:119577-28-5
- 2-Hydroxyquinoxaline
Catalog No.:BCC8577
CAS No.:1196-57-2
- GSK2190915 sodium salt
Catalog No.:BCC5588
CAS No.:1196070-26-4
- PF-3845
Catalog No.:BCC2326
CAS No.:1196109-52-0
- Olprinone Hydrochloride
Catalog No.:BCC1821
CAS No.:119615-63-3
- Sulfo-NHS-Biotin
Catalog No.:BCC3576
CAS No.:119616-38-5
- Arecaidine but-2-ynyl ester tosylate
Catalog No.:BCC6627
CAS No.:119630-77-2
- Naloxone benzoylhydrazone
Catalog No.:BCC5757
CAS No.:119630-94-3
- Moguisteine
Catalog No.:BCC4925
CAS No.:119637-67-1
N,N-dimethylsphingosine attenuates myocardial ischemia-reperfusion injury by recruiting regulatory T cells through PI3K/Akt pathway in mice.[Pubmed:27048490]
Basic Res Cardiol. 2016 May;111(3):32.
N,N-Dimethylsphingosine (DMS) has been documented to be in vitro protective against myocardial ischemia-reperfusion injury (IRI) and can recruit CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs), which may participate in the cardioprotection. We hypothesized that when in vivo applied after a myocardial ischemia, DMS may be cardioprotective by recruiting Tregs. Myocardial IRI was induced in C57BL/6 mice by occluding the left main coronary arteries followed by relaxation, and DMS (0.43 mg/kg) was intravenously injected 5 min after the onset of ischemia. We found that in wild-type (WT) mice, compared with the ischemia-reperfusion group, DMS reduced the infarct size (47.1 +/- 8.9 vs. 33.1 +/- 3.4 %, p < 0.01), and neutrophil infiltration at 24 h reperfusion (R) evaluated by TTC and immunohistochemical staining, respectively, and increased the aggregation of Tregs [(6 +/- 1)/mm(2) vs. (30 +/- 4)/mm(2), p < 0.01], peaking at 1 h R by immunofluorescence staining, with reduced gene expression of inflammatory factors at 4 h R in the reperfused myocardium by real-time PCR. This protection was abolished by phosphatidylinositol 3-kinase (PI3K)/Akt inhibitor or Tregs-depleting antibody. Relative to WT mice, the cardioprotection conferred by T cell- and B cell- deficient Rag2 knockout (KO) mice was not strengthened by DMS or by DMS and the adoptive transfer of Tregs from WT mice, but was abolished by DMS and WT non-Tregs and was recaptured by the cotransfer with WT Tregs but not with Akt1(+/-) mice-derived Tregs. In conclusion, applied at an early stage of ischemia, DMS may be in vivo protective against myocardial IRI by recruiting Tregs via PI3K/Akt pathway.
The sphingosine kinase inhibitor N,N-dimethylsphingosine inhibits neointimal hyperplasia.[Pubmed:20015089]
Br J Pharmacol. 2010 Feb 1;159(3):543-53.
BACKGROUND AND PURPOSE: Sphingosine-1-phosphate and its receptors may be involved in vascular smooth muscle cell (VSMC) proliferation following vascular injury. Here, we evaluate the effect of d-erythro-N,N-Dimethylsphingosine (DMS), a sphingosine kinase (SK) inhibitor, on VSMC proliferation, apoptosis and neointimal formation. EXPERIMENTAL APPROACH: Growth responses in vitro to fetal calf serum (FCS) were measured by [(3)H]-thymidine incorporation and extracellular signal-regulated kinase-1/2 (ERK-1/2) activation in quiescent primary cultures of porcine VSMC in the presence and absence of various concentrations of the SK inhibitor DMS. In vivo treatment with DMS was delivered with a local endoluminal catheter, following balloon injury of coronary arteries. The artery intimal formation was investigated by angiography, myography and histomorphometry. KEY RESULTS: In vitro experiments indicated that DMS induced a dose-dependent reduction in [(3)H]-thymidine incorporation and ERK-1/2 activation via a protein kinase C (PKC) independent mechanism with an IC(50) value of 12 +/- 6 and 15 +/- 10 microM respectively. DMS also reduced Akt signalling. Four weeks following in vivo delivery of DMS, complete functional endothelial regeneration was observed in all treatment groups, with significant reduction of intimal formation (vehicle 23.7 +/- 4.6% vs. DMS infusion 8.92 +/- 2.9%, P < 0.05). CONCLUSIONS AND IMPLICATIONS: Taken together, these results demonstrate that local administration of the SK inhibitor, DMS, reduced neointimal formation, and this effect could involve inhibition of ERK-1/2 and Akt signalling, and modulation of smooth muscle growth.
N,N-Dimethylsphingosine conjugates of poly-L-glutamic acid: synthesis, characterization, and initial biological evaluation.[Pubmed:19097786]
Bioorg Med Chem Lett. 2009 Feb 1;19(3):1012-7.
Poly-L-glutamic acid (PGA) has previously been demonstrated to be an effective backbone for creating a hydrophilic prodrug of the established anti-tumor agent, paclitaxel, the active agent in Taxol; this approach has obviated the need for the toxic Cremophor excipient, used to enhance the solubility of paclitaxel in the clinical formulation. In order to form hydrophilic prodrugs of the hydrophobic pro-apoptotic sphingolipid, N,N-Dimethylsphingosine (DMSP), PGA was condensed with DMSP, previously modified with coumarin to allow spectroscopic detection during conjugate synthesis, to yield PGA-DMSP. Conjugates with different loadings of DMSP were prepared and evaluated for in vitro cytotoxicity against two human breast adenocarcinoma cell lines. Time- and loading-dependent expression of cytotoxicity was observed, such that endpoints essentially equivalent to those observed with free-DMSP were achieved, but in a more protracted manner, consistent with prodrug behavior. PGA-DMSP was initially evaluated for toxicity in female nude mice, and administration of high net levels of DMSP, exceeding those achievable with free-DMSP, was well-tolerated. We propose that PGA-DMSP conjugates merit evaluation for anti-tumor efficacy in pre-clinical tumor models.
N,N-dimethylsphingosine-coumarin: synthesis, chemical characterization, and biological evaluation.[Pubmed:17432826]
Bioconjug Chem. 2007 May-Jun;18(3):731-5.
Coumarin derivatives of N,N-Dimethylsphingosine (DMSP) were prepared and chemically characterized. They were apparently biologically equivalent to DMSP in terms of tumor cell cytotoxicity and were used to establish the rapid mitochondrial localization of this sphingolipid in tumor cells, followed closely by its marked reduction of mitochondrial membrane potential.
Metabolomics implicates altered sphingolipids in chronic pain of neuropathic origin.[Pubmed:22267119]
Nat Chem Biol. 2012 Jan 22;8(3):232-4.
Neuropathic pain is a debilitating condition for which the development of effective treatments has been limited by an incomplete understanding of its chemical basis. We show by using untargeted metabolomics that sphingomyelin-ceramide metabolism is altered in the dorsal horn of rats with neuropathic pain and that the upregulated, endogenous metabolite N,N-Dimethylsphingosine induces mechanical hypersensitivity in vivo. These results demonstrate the utility of metabolomics to implicate unexplored biochemical pathways in disease.
N,N-Dimethylsphingosine is a potent competitive inhibitor of sphingosine kinase but not of protein kinase C: modulation of cellular levels of sphingosine 1-phosphate and ceramide.[Pubmed:9737868]
Biochemistry. 1998 Sep 15;37(37):12892-8.
Sphingosine 1-phosphate (SPP), a lipid second messenger formed by the action of sphingosine kinase, has been implicated in regulating diverse biological processes, including growth, survival, and differentiation. N,N-Dimethylsphingosine (DMS) inhibits sphingosine kinase and has been used to investigate the biological roles of SPP; however, little is known of the mechanism of inhibition of sphingosine kinase by DMS. In addition, DMS has been shown to inhibit protein kinase C in vitro. Here we report that DMS is a competitive inhibitor of sphingosine kinase from U937 monoblastic leukemia cells, Swiss 3T3 fibroblasts, and PC12 pheochromocytoma cells. DMS decreases basal levels of SPP and prevents increases in SPP in response to physiological stimuli known to activate sphingosine kinase. DMS also effectively increases cellular levels of ceramide in a variety of cell types, and resetting of the ceramide/SPP rheostat may account for the pro-apoptotic effects of DMS. Moreover, DMS, at concentrations which effectively inhibit sphingosine kinase, has no effect on protein kinase C activity or its membrane translocation. Thus, DMS acts as a specific competitive inhibitor of sphingosine kinase in diverse cell types and is a useful tool to elucidate the role of SPP as an intracellular second messenger.
N,N-dimethylsphingosine inhibition of sphingosine kinase and sphingosine 1-phosphate activity in human platelets.[Pubmed:8555236]
Biochemistry. 1996 Jan 16;35(2):626-33.
Potential sphingosine (Sph) metabolites include phosphorylated, N-acylated, and N-methylated derivatives. Phosphorylated Sph, i.e., sphingosine 1-phosphate (Sph-1-P), may act as an autocrine stimulator of blood platelets, as it is abundantly stored in platelets and released extracellularly and its exogenous addition induces platelet activation. In this study, we evaluated Sph-1-P formation and its effects in human platelets in the presence of other Sph metabolites. On addition of [3H]Sph to intact platelets, the label was rapidly converted to Sph-1-P. This conversion into [3H]Sph-1-P was inhibited by N,N-Dimethylsphingosine (DMS) in a dose-dependent manner, but not by other structurally related Sph derivatives, including ceramide. The inhibition of Sph-1-P formation by DMS was reproduced using a cell-free system (Sph kinase obtained from platelet cytosolic fractions) and much stronger than that by DL-threo-dihydrosphingosine, which had been considered to be the strongest inhibitor of Sph kinase. Administration of DMS to intact platelets resulted in a decrease in Sph-1-P mass and an increase in Sph mass. Furthermore, DMS inhibited the release of Sph-1-P from platelets stimulated with 12-O-tetradecanoylphorbol 13-acetate and inhibited platelet aggregation induced by exogenous addition of Sph-1-P. Collectively, our results indicate that DMS is useful as a Sph kinase inhibitor and that Sph-1-P actions as an autocrine stimulator of platelets are inhibited by DMS.