Sodium Monofluorophosphate phosphatase inhibitor

Acadesine (500 μM) increases the ZMP content in extracts of isolated hepatocytes after up to 30-40 min treatment, then remains fairly constant at approximately 4 nmol/g. This compound causes a transient 12-fold activation of AMPK at 15 min in rat hepatocytes and 2-3 fold activation of AMPK in adipocytes, without affecting levels of ATP, ADP or AMP. It also causes a dramatic inhibition of both fatty acid and sterol synthesis in rat hepatocytes, as well as a dramatic inactivation of HMG-CoA reductase. [1] AICAR induces apoptosis of B-CLL cells in a dose-dependent manner with EC50 of 380 μM. At 0.5 mM, it decreases cell viability of B-CLL cells from 20 representative patients from 68% to 26%, and induces caspase activation and cytochrome c release from mitochondria. Uptake and phosphorylation of the compound are required to induce apoptosis and activate AMPK in B-CLL cells. While concentrations of 2-4 mM only slightly affect the viability of T cells from B-CLL patients, 0.5 mM remarkably reduces viability of B cells but not T cells. [2] It triggers loss of cell Metabolism in K562, LAMA-84 and JURL-MK1 and is also effective in killing resistant K562 cells and Ba/F3 cells carrying the T315I-BCR-ABL mutation. The effect of AICAR is abrogated by GF109203X and Ro-32-0432, both inhibitor of classical and new PKCs and accordingly, it triggers relocation and activation of several PKC isoforms in K562 cells. The compound dose-dependently inhibits K562 colony formation at day 10, the growth inhibitory effect is already detected at 0.25 mM and is maximal at 2.5 mM. [3] AICAR causes a concentration-related reduction in CD18 expression on LPS-stimulated neutrophils in vitro. [4] It significantly (1 mM) inhibits N-formyl-methionyl-leucyl-phenylalanine-induced granulocyte CD11b up-regulation by a mean of 61% in blood. [5]

Monofluorophosphate displays potent activity on bone immobilization in vivo. Rats supplied with drinking water containing 50 ppm F as Monofluorophosphate show a significant increase in the bone thickness of mobile tibia and immobile tibia, compared with fluoride-free water group (1.48 vs 0.98 mm, 0.79 vs 0.40 mm, respectively). Monofluorophosphate does not change the specific gravities of the immobilized and non-immobilized tibiae of the rats. Administration of Monofluorophosphate increases the mineralization rate of bones and counteracts the decrease in bone thickness, ash content and specific gravity induced by immobilization, without changing the Ca/P ratio of the ash. [3]