(+)-D-threo-PDMP (hydrochloride)

(+)-D-threo-PDMP is a ceramide analog and is one of the four possible stereoisomers of PDMP (Item No. 62595).¹ (+)-D-threo-PDMP is an inhibitor of glucosylceramide synthase.^2,3 It inhibits glucosylceramide synthase by 50% when used at a concentration of 5 μM in an enzyme assay.³ (+)-D-threo-PDMP is the active component of racemic DL-threo-PDMP (Item No. 10005276). In vitro, (+)-D-threo-PDMP inhibits the synthesis of glucosylceramide synthase and lactosylceramide in B16 melanoma cells when used at a concentration of 25 µM and inhibits cell binding to laminin and collagen when used at concentrations of 10 and 25 µM.⁴ It also inhibits β-1,4-galactosyltransferase 6 (B4GALT6) and prevents lactosylceramide synthesis, which is a promotor of neuroinflammation in mice during chronic experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis.⁵ (+)-D-threo-PDMP inhibits ganglioside biosynthesis, reduces long-term potentiation (LTP) in mouse hippocampal CA1 neurons, and impairs learning in the four-pellet taking test in mice.⁶ [Matreya, LLC. Catalog No. 1756]

WARNING This product is not for human or veterinary use.

1. Vunnam, R.R., and Radin, N.S. Analogs of ceramide that inhibit glucocerebroside synthetase in mouse brain. Chem. Phys. Lipids 26(3), 265-278 (1980).

2. Abe, A., Inokuchi, J.-i., Jimbo, M., et al. Improved inhibitors of glucosylceramide synthase. J. Biochem. 111(2), 191-196 (1992).

3. Inokuchi, J.i., and Radin, N.S. Preparation of the active isomer of 1-phenyl-2-decanoylamino-3-morpholino-1-propanol, inhibitor of murine glucocerebroside synthetase. J. Lipid Res. 28(5), 565-571 (1987).

4. Inokuchi, J.-I., Momosaki, K., Shimeno, H., et al. Effects of D-threo-PDMP, an inhibitor of glucosylceramide synthetase, on expression of cell surface glycolipid antigen and binding to adhesive proteins by B16 melanoma cells. J. Cell. Physiol. 141(3), 573-583 (1989).

5. Mayo, L., Trauger, S.A., Blain, M., et al. Regulation of astrocyte activation by glycolipids drives chronic CNS inflammation. Nat. Med. 20(10), 1147-1156 (2014).

6. Fujiwara, H., Ikarashi, K., Yamazaki, Y., et al. Impairment of hippocampal long-term potentiation and failure of learning in mice treated with D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol. Biomed Res. 33(5), 265-271 (2012).