PDMP is a ceramide analog first prepared in a search for inhibitors of glucosylceramide synthase. PDMP has two adjacent chiral centers (C1 and C2) allowing for the formation of four possible isomers. PDMP contains all four of these stereoisomers. PDMP inhibits glucosylceramide synthase by 90% when used at a concentration of 0.8 μM in MDCKcell homogenates, however, 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. PDMP enhances curcumin-induced inhibition of proliferation, JNK activation, and Akt inhibition, as well as induction of apoptosis in WM-115 melanoma cells in vitro.
D-threo-PPMP is a glucosylceramide (GlyCer) synthetase inhibitor.1,2It is the active enanantiomer and enzymatic inhibitory component of the racemic DL-threo-PPMP . In MDCK kidney epithelial cells, D-threo-PPMP induces a 70% reduction in cell growthin vitroat 20 μM and significantly inhibits DNA synthesis at 3 μM.3[Matreya, LLC. Catalog No. 1865] 1.Shen, W., Henry, A.G., Paumier, K.L., et al.Inhibition of glucosylceramide synthase stimulates autophagy flux in neuronsJ. Neurochem.129(5)884-894(2014) 2.Lee, L., Abe, A., and Shayman, J.A.Improved inhibitors of glucosylceramide synthaseJ. Biol. Chem.274(21)14662-14669(1999) 3.Abe, A., Inokuchi, J.-i., Jimbo, M., et al.Improved inhibitors of glucosylceramide synthaseJ. Biochem.111(2)191-196(1992)
C2 Adamantanyl globotriaosylceramide (AdaGb3) is a bioactive sphingolipid and water-soluble form of globotriaosylceramide that contains an adamantanyl group in place of the fatty acyl chain. It inhibits Vero toxin binding to globotriaosylceramide in an ELISA assay when used at a concentration of 10 μM. AdaGb3 decreases cell surface expression of P-glycoprotein (P-gp) and reduces efflux of rhodamine 123 in MDCKcells. It also increases apical-to-basal transport of vinblastine in human intestinal C2BBe1 cells.
Herquline A is an alkaloid fungal metabolite originally isolated from P. herquei. It inhibits cell death induced by influenza A strain A PR 8 34 in MDCKcells with an IC50 value of 10 μg ml and inhibits viral replication in a plaque assay in a concentration-dependent manner. Herquline A also inhibits platelet aggregation induced by ADP and platelet-activating factor (PAF) in vitro (IC50s = 180 and 240 μM, respectively).