DL-PDMP

DL-PDMP is a ceramide analog first prepared in a search for inhibitors of UGCG (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. Treatment of cultured cells with PDMP reduces the synthesis of sphingosine and its derivatives, increases cellular ceramide, and induces cell cycle arrest. The ability to inhibit UGCG (glucosylceramide synthase) has been found to reside in the D-threo (1R,2R) enantiomer. Other activities, such as ASAH (alkaline ceramidase) inhibition and cytotoxicity, may involve interactions between PDMP isomers and/or direct activities of the other three isomeric PDMP compounds. PDMP blocks the glucosylation of ceramide by inhibiting UGCG (UDP-glucose:ceramide glucosyltransferase (glucosylceramide synthetase)). It inhibits the expression of cell surface glycolipid antigens and inhibits the growth of cultured rabbit skin fibroblasts. It possesses antitumor activity and inhibits Lewis lung carcinoma cell metastasis in vitro. It is a useful tool for studying the effects of cellular glycosphingolipid depletion. Enhances the apoptotic response to ionizing radiation by enhancing the ceramide signal. PDMP closely resembles the natural sphingolipid substrate of brain glucosyltransferase and acts as a potent and competitive inhibitor of this enzyme. Blocks the outgrowth of neurites and inhibits glycolipid synthesis in cultured NIH/3T3 cells.