Molecular Weight (MW)

258.23

Formula

C9H14N4O5

CAS No.

2627-69-2

Storage

-20℃ for 3 years in powder form

-80℃ for 2 years in solvent

Solubility (In vitro)

DMSO: 51 mg/mL (197.5 mM)

Water: <1 mg/mL

Ethanol: <1 mg/mL

Other info

Chemical Name: 1H-Imidazole-4-carboxamide, 5-amino-1-(5-O-phosphono-beta-D-ribofuranosyl)- (9CI)
InChi Key: NOTGFIUVDGNKRI-UUOKFMHZSA-N
InChi Code: 1S/C9H15N4O8P/c10-7-4(8(11)16)12-2-13(7)9-6(15)5(14)3(21-9)1-20-22(17,18)19/h2-3,5-6,9,14-15H,1,10H2,(H2,11,16)(H2,17,18,19)/t3-,5-,6-,9-/m1/s1
SMILES Code: c1nc(c(n1[C@H]2[C@@H]([C@@H]([C@H](O2)COP(=O)(O)O)O)O)N)C(=O)N

Synonyms

AICA ribonucleotide, AICA riboside, AICAR; Acadesine; AICA Riboside; ARA100; ARA-100; ARA 100; GP 1 110; SCH-900395; SCH 900395; SCH900395; AICAR

In Vitro

In vitro activity: 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.

Kinase Assay: AICAR is a cell-permeable AMP-activated protein kinase (AMPK) activator.

Cell Assay: Acadesine is added to K562 cell lines or primary cells (103 CD34+ cells/mL) growing in semisolid methyl cellulose medium. MethoCult H4100 or H4236 are used for cell lines and primary CD34+ cells respectively. Colonies are detected after 10 days of culture by adding 1 mg/mL of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reagent and are scored by Image J quantification software.

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.

Animal model

Mouse xenograft model of K562 cells

Formulation & Dosage

Dissolved in 0.9% NaCl; 50 mg/kg; i.p. administration

References

Eur J Biochem. 1995 Apr 15;229(2):558-65; PLoS One. 2009 Nov 18;4(11):e7889; Surgery. 1996 Mar;119(3):302-15..