Description
Acadesine results in accumulation of ZMP, which mimics the stimulating effect of AMP on AMPK and AMPK. Phase 3.
Alias
AICAR, AICA-riboside
Storage
2 years -20 centigrade Powder; 2 weeks 4 centigrade in DMSO; 6 months -80 centigrade in DMSO.
Synonyms
AICAR, AICA-riboside
Molecular Formula
C9H14N4O5
Chemical Name
5-amino-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)-tetrahydrofuran-2-yl)-1H-imidazole-4-carboxamide
Solubility
DMSO 2 mg/mL; Water <1 mg/mL; Ethanol <1 mg/mL
In vitro
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. Acadesine (500 μM) 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. Acadesine (500 μM) causes a dramatic inhibition of both fatty acid and sterol synthesis in rat hepatocytes. Acadesine (500 μM) also causes a dramatic inactivation of HMG-CoA reductase. Acadesine induces apoptosis of B-CLL cells in a dose-dependent manner with EC50 of 380 μM. Acadesine (0.5 mM) decreases cell viability of B-CLL cells from 20 representative patients from 68% to 26%. Acadesine (0.5 mM) induces caspase activation and cytochrome crelease from mitochondria. Uptake and phosphorylation of Acadesine (0.5 mM) are required to induce apoptosis and activate AMPK in B-CLL cells. Acadesine (2-4 mM) only slightly affects the viability of T cells from B-CLL patients, Acadesine (0.5 mM) remarkedly reduces viability of B cells but not T cells.Acadesine triggers loss of cell metabolism in K562, LAMA-84 and JURL-MK1 and is also effective in killing imatinib-resistant K562 cells and Ba/F3 cells carrying the T315I-BCR-ABL mutation. The effect of Acadesine is abrogated by GF109203X and Ro-32-0432, both inhibitor of classical and new PKCs and accordingly, Acadesine triggers relocation and activation of several PKC isoforms in K562 cells. Acadesine dose-dependently inhibits K562 colony formation at day 10, the growth inhibitory effect of acadesine is already detected at 0.25 mM and is maximal at 2.5 mM.Acadesine causes a concentration-related reduction in CD18 expression on LPS-stimulated neutrophils in vitro.Acadesine significantly (1 mM) inhibits N-formyl-methionyl-leucyl-phenylalanine-induced granulocyte CD11b up-regulation by a mean of 61% in blood.
In vivo
Acadesine (50 mg/kg) significantly reduces tumor formation in a mouse xenograft model of K562 cells.Acadesine (10 mg/kg) results in higher fluid required to stabilize hemodynamics in pigs. Acadesine (10 mg/kg) inhibits LPS-induced protein permeability of pulmonary capillaries, peak inspiratory pressures on constant tidal volume and dead space ventilation in pigs.
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