Antibodies
Acadesine
- 貨號 Cat. No.
- S1802
- 規格 Size
- 50mgã€200mg
- 品牌 Brand
- Selleckchem
Description
Acadesine
Catalog No.S1802
Acadesine results in accumulation of ZMP, which mimics the stimulating effect of AMP on AMPK and AMPK kinase. Phase 3.
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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
| Description | Acadesine results in accumulation of ZMP, which mimics the stimulating effect of AMP on AMPK and AMPK kinase. Phase 3. | |||||
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| Targets | AMPK | AMPK kinase | ||||
| IC50 | ||||||
| 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] | |||||
| 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] | |||||
| Features | A potential first-in-class adenosine regulating agent (ARA). | |||||
Protocol(Only for Reference)
Cell Assay: [3]
| 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. |
Animal Study: [3]
| Animal Models | mouse xenograft model of K562 cells |
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| Dosages | 50 mg/kg |
| Administration | Injected intraperitoneally |
| Solubility | 30% propylene glycol, 5% Tween 80, 65% D5W, 30 mg/mL |
References
Clinical Trial Information( data from http://clinicaltrials.gov)
| NCT Number | Recruitment | Conditions | Sponsor /Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT00559624 | Completed | Leukemia, B-Cell, Chronic | Advancell - Advanced In Vitro Cell Technologies, S.A.|Nexus Oncology Ltd | 2007-12 | Phase 1|Phase 2 |
| NCT00872001 | Terminated | Coronary Artery Bypass|Myocardial Infarction|Ventricular Dysfunction, Left|Stroke|Cardiopulmonary Bypass | Merck|Duke Clinical Research Institute | 2009-04 | Phase 3 |
| NCT01813838 | Not yet recruiting | SMD | Groupe Francophone des Myelodysplasies|Advancell - Advanced In Vitro Cell Technologies, S.A. | 2013-06 | Phase 1|Phase 2 |
Chemical Information
| Molecular Weight (MW) | 258.23 |
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| Formula | C9H14N4O5 |
| CAS No. | 2627-69-2 |
| Storage | 3 years -20℃Powder |
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| 6 months-80℃in DMSO | |
| Syonnyms | AICAR, AICA-riboside |
| Solubility (25°C) * | In vitro | DMSO | 2 mg/mL (7 mM) |
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| Water | <1 mg/mL (<1 mM) | ||
| Ethanol | <1 mg/mL (<1 mM) | ||
| In vivo | 30% propylene glycol, 5% Tween 80, 65% D5W, | 30 mg/mL | |
| * <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 Name | 5-amino-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)-tetrahydrofuran-2-yl)-1H-imidazole-4-carboxamide |
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