D,L-threo-1-Phenyl-2-decanoylamino-3-morpholino-1-propanol HCl

DL-threo PDMP is a mixture of ceramide analogs that contains two of the four possible stereoisomers of PDMP : D-threo-(1R,2R)-PDMP and L-threo-(1S,2S)-PDMP. DL-threo-PDMP inhibits glucosylceramide synthase by 33 and 48% in MDCK cell homogenates when used at concentrations of 5 and 10 μM. It reduces the synthesis of glucosylceramide, increases cellular ceramide, and induces cell cycle arrest in vitro. The ability to inhibit glucosylceramide synthase has been found to reside in the D-threo-(1R,2R) enantiomer. The D-threo-PDMP enantiomer is also responsible for inhibition of β-1,4-galactosyltransferase 6 and prevention of lactosylceramide synthesis, which is a promotor of neuroinflammation in mice during chronic experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. DL-threo-PDMP increases amyloid-β (1-42) (Aβ42) and Aβ39 production independent of ceramide metabolism via modulation of γ-secretase activity in HEK293 cells expressing the γ-secretase substrate SC100. [Matreya, LLC. Catalog No. 1719]

DL-threo-PDMP can deplete cells and mice of their glucosphinolipids.

Glucosylceramide synthase inhibitor; blocks formation of glucosylceramide from ceramide.

[1] RANGA RAO VUNNAM  Norman S R. Analogs of ceramide that inhibit glucocerebroside synthetase in mouse brain[J]. Chemistry and Physics of Lipids, 1980, 26 3: Pages 265-278. DOI: 10.1016/0009-3084(80)90057-2
[2] J INOKUCHI  N S R. Preparation of the active isomer of 1-phenyl-2-decanoylamino-3-morpholino-1-propanol, inhibitor of murine glucocerebroside synthetase.[J]. Journal of Lipid Research, 1987, 28 5: 565-571.
[3] C S RANI. Cell cycle arrest induced by an inhibitor of glucosylceramide synthase. Correlation with cyclin-dependent kinases.[J]. The Journal of Biological Chemistry, 1995, 270 6: 2859-2867. DOI: 10.1074/jbc.270.6.2859
[4] A ABE. Structural and stereochemical studies of potent inhibitors of glucosylceramide synthase and tumor cell growth.[J]. Journal of Lipid Research, 1995, 36 3: 611-621.
[5] LIOR MAYO. Regulation of astrocyte activation by glycolipids drives chronic CNS inflammation[J]. Nature Medicine, 2014, 20 10: 1147-1156. DOI: 10.1038/nm.3681
[6] NOBUMASA TAKASUGI . Synthetic ceramide analogues increase amyloid-β 42 production by modulating γ-secretase activity[J]. Biochemical and biophysical research communications, 2015, 457 2: Pages 194-199. DOI: 10.1016/j.bbrc.2014.12.087