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PDMP is a ceramide analog first prepared in a search for inhibitors of glucosylceramide synthase.1 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.2 The ability to inhibit glucosylceramide synthase has been found to reside in the D-threo (1R,2R) enantiomer.3 Other activities, such as alkaline ceramidase inhibition and cytotoxicity, may involve interactions between PDMP isomers and/or direct activities of the other three isomeric PDMP compounds.4
1
Vunnam, R.R., and Radin, N.S. Analogs of ceramide that inhibit glucocerebroside synthetase in mouse brain. Chem Phys Lipids26265-278(1980).
2
Rani, C.S.S., Abe, A., Chang, Y., et al. Cell cycle arrest induced by an inhibitor of glucosylceramide synthase. Correlation with cyclin-dependent kinases. J Biol Chem270(6)2859-2867(1995).
3
Abe, A., Radin, N.S., Shayman, J.A., et al. Structural and stereochemical studies of potent inhibitors of glucosylceramide synthase and tumor cell growth. J Lipid Res36611-621(1995).
4
Bielawska, A., Greenberg, M.S., Perry, D., et al. (1S,2R)-D-erythro-2-(N-myristoylamino)-1-phenyl-1-propanol as an inhibitor of ceramidase. J Biol Chem27112646-12654(1996).
Vunnam, R.R., and Radin, N.S. Analogs of ceramide that inhibit glucocerebroside synthetase in mouse brain. Chem Phys Lipids26265-278(1980).
Rani, C.S.S., Abe, A., Chang, Y., et al. Cell cycle arrest induced by an inhibitor of glucosylceramide synthase. Correlation with cyclin-dependent kinases. J Biol Chem270(6)2859-2867(1995).
Abe, A., Radin, N.S., Shayman, J.A., et al. Structural and stereochemical studies of potent inhibitors of glucosylceramide synthase and tumor cell growth. J Lipid Res36611-621(1995).
Bielawska, A., Greenberg, M.S., Perry, D., et al. (1S,2R)-D-erythro-2-(N-myristoylamino)-1-phenyl-1-propanol as an inhibitor of ceramidase. J Biol Chem27112646-12654(1996).