SPHINGOLIPIDS

The sphingolipid cycle encompasses a large family of biomolecules which play unique and diverse roles in signal transduction. In a process analogous to the phospholipase C- mediated production of diacylglycerols, sphingomyelinase hydrolyzes sphingomyelin (see Scheme 9) producing ceramide, a second messenger which can stimulate protein phosphatase 2A¹, MAP kinase² and induce apoptosis^3,4,26. Ceramide may be converted, via ceramidase, to sphingosine, which displays a variety of activities, or phosphorylated to ceramide 1-phosphate⁵. Sphingosine can be converted to sphingosine-1-phosphate which is mitogenic and stimulates calcium release from intracellular stores⁶. Inducers of sphingomyelin breakdown and release of sphingoid second messengers include TNF-a^7,8, g-interferon⁹, IL-1¹⁰, 1a,25-dihydroxyvitamin D₃¹¹, complement components¹² and diverse forms of cellular stress¹⁸ For recent reviews on sphingolipids in cellular signalling see references 13-18.

SPHINGOLIPIDS

SL-100
C₂ Ceramide
N-Acetylsphingosine, D-erythro
98%, MW=341.5 [3102-57-6] Storage: -20°C
N-Acetylsphingosine is a biologically active, cell permeable ceramide analog. It inhibits cell proliferation and induces monocytic differentiation of HL-60 cells¹⁹ and induces apoptosis^20,21. It stimulates protein phosphatase 2A¹, activates MAP kinase² and SAP kinase²² and induces PKCd and e translocation²³. Physiological levels of C₂ ceramide, produced by the action of a PAF:sphingosine CoA-independent transacetylase, have been detected in HL-60 cells²⁴.
5 mg
25 mg

SL-110
C₆ Ceramide
N-Hexanoylsphingosine, D-erythro
98%, MW=397.7 [124753-97-5] Storage: -20°C
A biologically active, cell permeable, but nonphysiologic ceramide analog. It stimulates protein phosphatase 2A at concentrations as low as 10 nM¹ and activates MAP kinase². It arrests Molt-4 leukemia cells in the G₀/G₁ phase²⁵, induces apoptosis²⁶, suppresses insulin-induced tyrosine phosphorylation²⁷ and inhibits glycoprotein traffic by the secretory pathway²⁸.
5 mg
25 mg

SL-112
C₈ Ceramide
N-Octanoylsphingosine, D-erythro
98%, MW=425.7, Storage: -20°C
A biologically active, cell permeable, but nonphysiologic ceramide analog. It induces phosphorylation on Thr-669 in A-431 cells by stimulation of ceramide-activated protein kinase²⁹. Stimulates IL-2 secretion¹⁰ and induces apoptosis²⁶.
5 mg
25 mg

SL-115
C₁₆ Ceramide
N-Palmitoylsphingosine, D-erythro
98%, MW=537.9 [24696-26-2] Storage: -20°C
An abundant molecular species of endogenous ceramide. It induces phosphorylation on Thr-669 in A-431 cells by stimulation of ceramide-activated protein kinase²⁹ and activates NF-kB at concentrations as low as 50 nM³⁰. Activates PKCz³¹.
5 mg
25 mg

SL-101
C₂ Dihydroceramide
N-Acetylsphinganine, D-erythro
98%, MW=343.5, Storage: -20°C
C₂ Dihydroceramide is inactive and may be used as a negative control for C₂ ceramide^20,32.
5 mg
25 mg

SL-111
C₆ Dihydroceramide
N-Hexanoylsphinganine, D-erythro
98%, MW=399.7, Storage: -20°C
C₆ Dihydroceramide is inactive and may be used as a negative control for C₆ ceramide²⁵.
5 mg
25 mg

SL-113
C₈ Dihydroceramide
N-Hexanoylsphinganine, D-erythro
98%, MW=425.7, Storage: -20°C
C₈ Dihydroceramide is inactive and may be used as a negative control for C₈ ceramide.
5 mg
25 mg

SL-142
C₈ Ceramide-1-phosphate, D-erythro
98%, MW=505.7, Storage: -20°C
Stimulates DNA synthesis when added exogenously to cultured fibroblasts at 5 µM. Mitogenic activity is antagonized by cell permeable ceramides³³.
1 mg
5 mg

SL-145
C₈ Ceramine, D-erythro
98%, MW=411.7, Storage: -20°C
C₈ ceramine is an analog of ceramide in which the amide is substituted with an amine. This substitution renders it inert to ceramidases. It is highly effective at induction of apoptosis in U937 cells. Ceramine induces peak DNA fragmentation in 6 hrs. compared to 18 hrs for C₈ ceramide³⁴.
1 mg
5 mg

SL-125
Dihydrosphingosine, D-erythro (Sphinganine)
98%, MW=301.5, Storage: -20°C
Biosynthetic precursor of sphingosine^35,36. Inhibits protein kinase C³⁷.
10 mg
50 mg

SL-143
Dihydrosphingosine-1-phosphate, D-erythro
98%, MW=381.5, Storage: -20°C
Saturated analog of sphingosine-1-phosphate displaying 20-fold lower activity. May be used as a negative control³⁸. Rapidly dephosphorylated by a sphingosine phosphatase in cultured human fibroblasts³⁹.
1 mg
5 x 1 mg

SL-105
N,N-Dimethylsphingosine, D-erythro
98%, MW=327.6 [119567-63-4] Storage: -20°C
N,N-Dimethylsphingosine blocks the conversion of sphingosine to sphingosine-1-phosphate by inhibiting sphingosine kinase⁴⁰. It stereospecifically induces EGF receptor autophosphorylation producing EGF-like activity in vitro in the absence of EGF⁴¹. It is produced endogenously via ceramide catabolism^41,42. It induces apoptosis⁴³ and has been shown to inhibit protein kinase C and enhance src-kinase activity⁴⁴.
5 mg
25 mg

SL-130
3-Ketosphingosine
MW=297.5
A useful precursor for the preparation radiolabeled sphingosine⁴⁵.
Inquire

SL-135
Sphingomyelin
From bovine brain. Contains primarily stearic and nervonic acids.
98%, MW=731.1 (stearoyl form) [85187-10-6] Storage: -20°C
Precursor to ceramide second messengers via the action of sphingomyelinase⁴⁶.
100 mg
500 mg

EI-155
Sphingosine, D-erythro
99%, MW=299.5 [123-78-4] Storage: -20°C
Sphingosine is a potent (IC₅₀=1-3 µM)³⁷ and selective inhibitor of protein kinase C. Inhibition is competitive with diacylglycerol, phorbol dibutyrate and Ca²⁺ and it also inhibits PKC activation by other lipids^47,48. It acts on an equimolar basis with 1,2-dioleoylglycerol and does not affect other kinases such as MLCK and PKA¹⁴. It is active in intact cells and has been identified as an endogenous constituent in HL-60 cells⁴⁹, neutrophils⁵⁰, rat liver and brain⁵¹ and mouse tissues⁵². Other activities include inhibition of phosphatidate phosphohydrolase⁵³, Na⁺,K⁺-ATPase⁵⁴, CTP:phosphocholine cytidylyltransferase⁵⁵, calmodulin-dependent enzymes⁵⁶, binding of factor VII to tissue factor⁵⁷, binding of thyrotropin releasing hormone to its receptor⁵⁸ and activation of EGF receptor kinase⁵⁹, phospholipase D⁶⁰ and casein kinase II⁶¹.
25 mg
100 mg

SL-140
Sphingosine-1-phosphate, D-erythro
98%, MW=379.5 [26993-30-6] Storage: -20°C
Sphingosine-1-phosphate is a putative second messenger that mobilizes calcium from intracellular stores via an IP₃ independent pathway⁶². This pathway is involved in IgE receptor (FceRI) mediated calcium mobilization⁶³. Other demonstrated effects include suppression of ceramide-mediated apoptosis⁶⁴, activation of the MAP kinase⁶⁵, activation of phospholipase D⁶⁶, inhibition of chemotactic motility and invasiveness of tumor cells⁶⁷ and stimulation of quiescent Swiss 3T3 fibroblast growth⁶⁸.
1 mg
5 x 1 mg

SL-141
Sphingosylphosphorylcholine, D-erythro
98%, MW=464.6 [1670-26-4] Storage: -20°C
Sphingosylphosphorylcholine induces release of Ca²⁺ from intracellular stores via an IP₃ independent pathway in permeabilized pancreatic acinar cells⁶⁹. It is an extremely potent mitogen in numerous cell types⁷⁰ and induces neurite outgrowth in mouse neuroblastoma cells⁷¹. It rapidly activates transcription factor AP-1⁷² and transiently activates MAP kinase⁷³.
10 mg
5 x 10 mg

SPHINGOLIPID REAGENTS

SL-200
L-Cycloserine
L-4-Amino-3-isoxazolidinone
99%, MW=102.1 [339-72-0] Storage: 0°C
L-Cycloserine blocks sphingosine biosynthesis by inhibition of ketosphinganine synthase⁷⁴. It enhances glycosphingolipid depletion by PDMP⁷⁵.
100 mg
500 mg

Diacylglycerol kinase
[93076-89-2] (EC 2.7.1.107) Storage: -20°C
From E. coli. Supplied at 1 mg/ml in potassium phosphate buffer, 20% glycerol, pH 7.0. Specific activity: >2 U/mg protein. Can be used to quantify ceramide in cell extracts^76,77,83.

SL-205
DL-threo-Dihydrosphingosine
98%, MW=301.5 [73938-69-9] Storage: -20°C
A potent, cell permeable, competitive inhibitor of sphingosine kinase⁷⁸. A useful tool to investigate sphingosine metabolism and the role of sphingosine-1-phosphate in signal transduction.
10 mg
50 mg

SL-220
Fumonisin B₁
98%, MW=721.8 [116355-83-0] Storage: -20°C
A fungal metabolite produced by Fusarium moniliforme. It Inhibits sphingolipid biosynthesis via inhibition of sphinganine N-acyltransferase. IC₅₀=0.1 µM in rat liver microsomes⁷⁹. Sphingomyelin biosynthesis is preferentially inhibited versus glycosphingolipids in neuronal cells⁸⁰. Blocks complex sphingolipid biosynthesis, altering cell-cell interactions and cell growth and viability⁸¹. A useful tool for studying sphingolipid function.
1 mg
5 mg
NEW LOWER PRICE

SL-219
Fumonisin B₂
98%, MW=705.8 [116355-84-1] Storage: -20°C
A fungal metabolite produced by Fusarium moniliforme. It Inhibits sphingolipid biosynthesis via inhibition of sphinganine N-acyltransferase. IC₅₀=0.1 µM in rat liver microsomes⁷⁹.
1 mg
5 mg

SL-221
MAPP, D-erythro
(1S,2R)-D-erythro-2-(N-Myristoylamino)-1-phenyl-1-propanol
98%, MW=361.6 [66085-59-4] Storage: -20°C
A cell-permeable and specific inhibitor of alkaline ceramidase, which can raise intracellular ceramide levels by blocking the hydrolysis of ceramide to sphingosine and free fatty acid⁸². Treatment of HL-60 cells at 5 µM, increased endogenous ceramide about three-fold in 24 hr. and suppressed cell proliferation. Has no effect on the activity of sphingomyelinases, other ceramide metabolizing enzymes or ceramide activated protein phosphatase⁸².
5 mg
25 mg

SL-222
MAPP, L-erythro
(1R,2S)-L-erythro-2-(N-Myristoylamino)-1-phenyl-1-propanol
98%, MW=361.6, Storage: -20°C
Useful as a negative control for D-erythro-MAPP. It does not raise endogenous ceramide levels or inhibit the growth of HL-60 cells¹³.
5 mg
25 mg

SL-225
3-O-Methyl-sphingomyelin
Inhibits neutral sphingomyelinase, IC₅₀=50 µM⁸³.
Inquire

SL-210
DL-PDMP
DL-threo-1-Phenyl-2-decanoylamino-3-morpholino-1-propanol
98%, MW=390.6 [73257-80-4] Storage: 0°C
PDMP blocks the glucosylation of ceramide by inhibiting UDP-glucose:ceramide glucosyltransferase (glucosylceramide synthetase)⁸⁴. It inhibits the expression of cell surface glycolipid antigens⁸⁵ and inhibits the growth of cultured rabbit skin fibroblasts⁸⁶. It possesses antitumor activity⁸⁷ and inhibits Lewis lung carcinoma cell metastasis in vitro⁸⁸. It is a useful tool for studying the effects of cellular glycosphingolipid depletion⁷⁵ (For a review see reference 89).
10 mg
50 mg

SL-215
DL-PPMP
DL-threo-1-Phenyl-2-palmitoylamino-3-morpholino-1-propanol
98%, MW=474.7 Storage: 0°C
Inhibits glucosylceramide synthetase. More effective than PDMP in intact cells⁹⁰.
5 mg
25 mg

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