L-690,488

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].

Signaling Pathways >> Metabolic Enzyme/Protease >> Phosphatase

Research Areas >> Metabolic Disease

Inositol monophosphatase (IMPase)[1][2]

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].

[1]. Atack JR, et al. Effects of L-690,488, a prodrug of the bisphosphonate inositol monophosphatase inhibitor L-690,330, on phosphatidylinositol cycle markers. J Pharmacol Exp Ther. 1994 Jul;270(1):70-6.

[2]. Chen X, et al. Stimulatory effect of lithium on glucose transport in rat adipocytes is not mediated by elevation of IP1. Am J Physiol. 1998 Aug;275(2):E272-7.