d-threo-pdmp

(+)-D-threo-PDMP is a ceramide analog and is one of the four possible stereoisomers of PDMP . (+)-D-threo-PDMP is an inhibitor of glucosylceramide synthase. It inhibits glucosylceramide synthase by 50% when used at a concentration of 5 μM in an enzyme assay. (+)-D-threo-PDMP is the active component of racemic DL-threo-PDMP .

D-threo-PDMP is a potent inhibitor of glucoceramide synthase (GCS), effectively reducing cell surface glycosphingolipids by inhibiting glycosylation. Additionally, it decreases the axon plexus's total length and the number of axon branch points, ultimately inhibiting neurite growth.

(-)-L-threo-PDMP is an enhancer of ganglioside biosynthesis. The (-)-L-threo-PDMP (1S,2S) isomer is the active stimulatory component of DL-threo-PDMP in contrast to (+)-D-threo-PDMP , which is an inhibitor of glucosylceramide synthetase. (-)-L-threo-PDMP upregulates GM3, GD3, and GQ1b synthase levels, which are glycosyltransferases involved in ganglioside biosynthesis, and increases ganglioside levels in cells. It increases neurite outgrowth and synapse formation in vitro and improves retention of a long-term memory learned prior to forebrain ischemia in rats when administered following ischemia at a dose of 40 mg/kg per day.

PDMP hydrochloride is a ceramide analog originally developed as an inhibitor of glucosylceramide synthase that contains four stereoisomers due to two adjacent chiral centers, and while total PDMP hydrochloride inhibits glucosylceramide synthase by approximately 90% at 0.8 μM in MDCK cell homogenates, the inhibitory activity resides in the D-threo (1R,2R) enantiomer, which also blocks β-1,4-galactosyltransferase 6, prevents lactosylceramide-driven neuroinflammation in experimental autoimmune encephalomyelitis, additionally, PDMP hydrochloride enhances curcumin-induced antiproliferative and pro-apoptotic effects in melanoma cells.