Inhibitor SourceBook™ Second Edition

Sphingomyelinase Inhibitors
Ceramide, a sphingosine-based lipid-signaling molecule,
has gained serious attention as an important signaling
molecule in cell cycle, cell differentiation, apoptosis, and
immune response. Ceramide is generated either through
de novo synthesis mediated by ceramide synthase or
through hydrolysis of membrane sphingomyelin by
an acid or neutral sphingomyelinase. Acid and neutral
sphingomelinases differ in their ion dependence, pH
optima, and cellular localization. Recent evidence
suggests that the activation of a non-specific lipid
scramblase during apoptosis induces the flipping of
sphingomyelin from the cell surface to the cytoplasm
side of the plasma membrane where it is cleaved by
neutral sphingomyelinase to generate ceramide. The
production of ceramide induces blebbing of the plasma
membrane and aids in rapid engulfment by phagocytes.
Neutral sphingomyelinase-released ceramide has also
been shown to be essential for capping of L-selectin in
lymphocytes.
Sphingomyelinase Inhibitors
Calbiochem • Inhibitor SourceBook
Lipid Signaling
Some evidence exists indicating that acid
sphingomyelinase deficient cells have defects in
apoptotic signaling pathways. Sphingomyelin is
usually rapidly broken down in the late endosomes and
lysosomes. Hence, in acid sphingomyelinase deficiency,
sphingomyelin may be kinetically trapped in lysosomes
and disrupt endocytic trafficking of raft-associated
cell surface signaling molecules. Defects in acid
sphingomyelinase have also been linked to lysosomal
storage disease known as Niemann-Pick disease, which
results in progressive enlargement of liver and spleen.
References:
Cremesti, A.E., et al. 2002. FEBS Lett. 531, 47.
Sillence, D.J. 200 . BMC Cell Biology 2, 24.
Zhang, Y., et al. 200 . J. Biol. Chem. 276, 775.
Tomiuk, S., et al. 998. Proc. Natl. Acad. Sci. USA 95, 3638.
Product Cat. No. Comments Size Price
Chlorpromazine,
Hydrochloride
215921 {2-Chloro-10-[3´-(dimethylamino)propyl]phenothiazine, HCl}
An inhibitor of calmodulin-dependent phosphodiesterase I (IC 50 = 7 mM) that
acts as an inhibitor of lysosomal sphingomyelinase.
3,4-Dichloroisocoumarin 287815 A serine protease inhibitor that blocks daunorubicin-induced neutral
sphingomyelinase activation.
Fumonisin B , Fusarium
moniliforme
344850 (FB 1 )
A cell-permeable mycotoxin that inhibits sphingolipid biosynthesis in rat kidney
and in liver microsomes by inhibition of sphingosine N-acyltransferase (ceramide
synthase; IC 50 = 00 nM). Preferentially inhibits sphingomyelin biosynthesis in
neuronal cells. Exhibits carcinogenic properties.
Gentamycin Sulfate 345814 A broad-spectrum antibiotic that reduces sphingomyelinase activity in
fibroblasts.
Manumycin A, Streptomyces
parvulus
444170 A potent and selective inhibitor of farnesyl transferase (IC 50 = 5 mM) that acts as
an irreversible inhibitor of neutral sphingomyelinase.
N-SMase Inhibitor, GW4869 567715 (GW554869A; GW69A; Sphingomyelinase, Neutral, Inhibitor GW4869)
A cell-permeable, symmetrical dihydroimidazolo-amide that acts as a potent,
specific, and non-competitive inhibitor of neutral sphingomyelinase (N-SMase)
(IC 50 = mM, rat brain N-SMase).
N a -Tosyl-Phe Chloromethyl
Ketone
Squalene-2,3-oxide Cyclase Inhibitor
616387 (TPCK)
A serine protease inhibitor that blocks daunorubicin-induced neutral
sphingomyelinase activator and sphingomyelin hydrolysis.
More online... www.calbiochem.com/inhibitors/sphingomyelinase
500 mg $57
0 mg $ 30
250 mg
g
mg $69
g $58
mg $77
mg $ 46
Product Cat. No. Comments Size Price
AMO 6 8 1712 Anticholesterolemic agent that can be used as an inhibitor of squalene-2,3-oxide
cyclase to study the action of squalene epoxidase in the microsomal cholesterol
biosynthetic pathway.
$39
$ 0
250 g $ 29
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