AICAR (Acadesine)

Catalog No.S1802 Synonyms: NSC105823

AICAR (Acadesine) Chemical Structure

Molecular Weight(MW): 258.23

AICAR (Acadesine), an AMPK activator, results in accumulation of ZMP, which mimics the stimulating effect of AMP on AMPK and AMPK kinase. Phase 3.

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2 Customer Reviews

  • British Journal of Pharmacology, 2015, 172(13):3284–3301.. AICAR (Acadesine) purchased from Selleck.

    Representative western blots and quantitative analysis of NRF-1 and TFAM (A), SOD2 and UCP2 (B).

    Sci Rep, 2016, 6:30272.. AICAR (Acadesine) purchased from Selleck.

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Biological Activity

Description AICAR (Acadesine), an AMPK activator, results in accumulation of ZMP, which mimics the stimulating effect of AMP on AMPK and AMPK kinase. Phase 3.
Features A potential first-in-class adenosine regulating agent (ARA).
Targets
AMPK [1]
(Cell-free assay)
AMPKK [1]
(Cell-free assay)
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. [1] 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. [2] 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. [3] Acadesine causes a concentration-related reduction in CD18 expression on LPS-stimulated neutrophils in vitro. [4] Acadesine significantly (1 mM) inhibits N-formyl-methionyl-leucyl-phenylalanine-induced granulocyte CD11b up-regulation by a mean of 61% in blood. [5]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
mouse 3T3L1 cells MWrGeY5kfGmxbjDhd5NigQ>? MVK1NFAh|ryP NFvEOmU2KGh? MYPBZ5RqfmG2aX;uJI9nKEGPUFugbY4hdW:3c3WgN3Q{VDFiY3XscJMh[XO|ZYPz[YQh[XNiQV3QT{BxcG:|cHjvdplt[XSrb36gZZQhPTByIIXNJIFnfGW{IEWgbJJ{KGK7IGfld5Rmem5iYnzveJRqdmdiYX7hcJl{cXN? M3TUOVI2OjZ{OUSw
mouse 3T3L1 cells NY\TToQ4TnWwY4Tpc44h[XO|YYm= MUiwMlIhdU1? M33pd|kh\GG7cx?= MnPLTY5kemWjc3WgbY4hSU2SS3HsdIhiKFSqckG3NkBxcG:|cHjvdplt[XSrb36gbY4hdW:3c3WgN3Q{VDFiY3XscJMh[XRiMD6yJI1OKGGodHXyJFkh\GG7czDifUBY\XO2ZYLuJIJtd3RibXX0bI9l NX20SndDOjZyOEizN|U>

... Click to View More Cell Line Experimental Data

In vivo Acadesine (50 mg/kg) significantly reduces tumor formation in a mouse xenograft model of K562 cells. [3] 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. [4]

Protocol

Cell Research:

[3]

+ Expand
  • Cell lines: K562 cell lines
  • Concentrations: 2.5 mM
  • Incubation Time: 10 days
  • Method:

    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.


    (Only for Reference)
Animal Research:

[3]

+ Expand
  • Animal Models: mouse xenograft model of K562 cells
  • Formulation: 0.9% NaCl
  • Dosages: 50 mg/kg
  • Administration: Injected intraperitoneally
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 51 mg/mL (197.49 mM)
Water <1 mg/mL
Ethanol <1 mg/mL
In vivo

* 1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 258.23
Formula

C9H14N4O5

CAS No. 2627-69-2
Storage powder
in solvent
Synonyms NSC105823

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT01813838 Terminated SMD Groupe Francophone des Myelodysplasies|Advancell - Advanced In Vitro Cell Technologies, S.A. June 2013 Phase 1|Phase 2
NCT00872001 Terminated Coronary Artery Bypass|Myocardial Infarction|Ventricular Dysfunction, Left|Stroke|Cardiopulmonary Bypass Merck Sharp & Dohme Corp.|Duke Clinical Research Institute April 2009 Phase 3
NCT00559624 Completed Leukemia, B-Cell, Chronic Advancell - Advanced In Vitro Cell Technologies, S.A.|Nexus Oncology Ltd December 2007 Phase 1|Phase 2

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AMPK Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID