L-690488

L-690488 is a prodrug of L-690330 and is a selective inositol monophosphatase (IMPase) inhibitor. L-690488 has more effective cell penetration than L-690330^[1][2]. IC50 & Target: Inositol monophosphatase (IMPase)^[1][2] In Vitro: The effects of L-690488 are studied in cholinergically (carbachol)-stimulated rat cortical slices and Chinese hamster ovary cells stably transfected with the human muscarinic m1 receptor (m1 CHO cells). The EC₅₀ values of L-690488 are 3.7 μM and 1.0 μM in rat cortical slices and m1 CHO cells, respectively). The time course and maximum accumulation of [³H] CMP-PA in L-690488-treated m1 CHO cells is similar to lithium but L-690488 is again much more potent (EC₅₀ values of 3.5 μM and 0.52 mM for L-690488 and lithium, respectively)^[1].
L-690488 attenuates the carbachol-induced elevation of inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate in m1 CHO cells. That these effects of L-690488 on the phosphatidylinositol (Pl) cycle are indeed due to inositol depletion^[1].