d-threo-pdmp

(+)-D-threo-PDMP is a ceramide analog and is one of the four possible stereoisomers of PDMP . (+)-D-threo-PDMP is an inhibitor of glucosylceramide synthase. It inhibits glucosylceramide synthase by 50% when used at a concentration of 5 μM in an enzyme assay. (+)-D-threo-PDMP is the active component of racemic DL-threo-PDMP .

D-threo-PDMP 为一有效的葡萄糖神经酰胺合成酶 (GCS) 抑制剂, 通过抑制糖基化作用减少细胞表面糖鞘脂，进而减少轴突丛总长度与轴突分支点数量，抑制神经突生长。

(-)-L-threo-PDMP is an enhancer of ganglioside biosynthesis. The (-)-L-threo-PDMP (1S,2S) isomer is the active stimulatory component of DL-threo-PDMP in contrast to (+)-D-threo-PDMP , which is an inhibitor of glucosylceramide synthetase. (-)-L-threo-PDMP upregulates GM3, GD3, and GQ1b synthase levels, which are glycosyltransferases involved in ganglioside biosynthesis, and increases ganglioside levels in cells. It increases neurite outgrowth and synapse formation in vitro and improves retention of a long-term memory learned prior to forebrain ischemia in rats when administered following ischemia at a dose of 40 mg/kg per day.

PDMP hydrochloride 是一种神经酰胺类似物，最初作为葡萄糖神经酰胺合成酶抑制剂开发，由于其含有两个相邻手性中心而存在四种立体异构体。在 MDCK 细胞匀浆中，总 PDMP hydrochloride 在 0.8 μM 条件下可抑制约 90% 的葡萄糖神经酰胺合成酶活性，其中抑制活性主要来源于 D-threo（1R,2R）对映体，该对映体同时抑制 β-1,4-半乳糖基转移酶 6，并在实验性自身免疫性脑脊髓炎模型中阻断乳糖神经酰胺介导的神经炎症。此外，PDMP hydrochloride 还能增强姜黄素在黑色素瘤细胞中的抗增殖和促凋亡作用。