D,L-threo-PPMP

This product is a glucosylceramide synthase inhibitor, an enzyme that is essential for the synthesis of a very large number of different glycolipids that are found in many organisms. PPMP has four possible isomers due to its two chiral centers (D-threo, L-threo, D-erythro, and L-erythro). Due to PPMP’s ability to inhibit the joining of ceramides with carbohydrates there can be an accumulation of ceramide in the cells and this can lead to apoptosis. This process has been suggested as a treatment for cancer since the addition of agents that retard ceramide glucosylation, such as PPMP, have been shown to increase cytotoxicity in tumor cells.1 Cells that were incubated with PPMP have been shown to have a 50% decrease in the viral fusion of HIV-1, causing a reduction in the penetration of this virus into these cells.2 PPMP has been used to arrest the growth of the malarial causing parasite Plasmodium falciparum by inhibiting its very specific glucosylceramide synthase, an approach that has great potential for malarial chemotherapy.3 In addition to its stereochemistry, the acyl chain of PPMP has a very marked effect on the intensity of the inhibitory action of the molecule. Conduritol beta epoxide (CBE), an inhibitor of betaglucosidase, and PPMP, an inhibitor of glucosylceramide synthase, can be used to create a model of Gaucher disease.4