Home PI3K/Akt/mTOR AMPK Activator AICAR (Acadesine)

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AICAR (Acadesine) AMPK Activator

Cat.nr.: S1802

AICAR (Acadesine, NSC105823, AICA Riboside), een AMPK activator, resulteert in accumulatie van ZMP, wat het stimulerende effect van AMP op AMPK en AMPK kinase nabootst. Deze verbinding induceert mitophagy. Fase 3.
AICAR (Acadesine) AMPK Activator Chemical Structure

Chemische structuur

Molecuulgewicht: 258.23

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Kwaliteitscontrole (Quality Control)

Batch: Zuiverheid: 99.97%
99.97

Producten die vaak samen worden gebruikt met AICAR (Acadesine)

Tanespimycin (17-AAG)

Treatment with this compound and 17-AAG reduces cell proliferation and affects chromosome segregation in MEFs and human cancer cells.

Nutlin-3a

Nutlin-3a shows no synergistic activity with this compound as it induces p53-independent apoptosis.

Celkweek, behandeling & werkzame concentratie
(Cell Culture, Treatment & Working Concentration)

Cellijnen Assaytype Concentratie Incubatietijd Formulering Activiteitsbeschrijving PMID
3T3L1 Function assay 0.2 mM 9 days Increase in AMPKalpha Thr172 phosphorylation in mouse 3T3L1 cells at 0.2 mM after 9 days by Western blot method 26088335
3T3L1 Function assay 500 μM 5 h Activation of AMPK in mouse 3T3L1 cells assessed as AMPK phosphorylation at 500 uM after 5 hrs by Western blotting analysis 25262940
C2C12 Function assay 1 mM 1 hr Activation of AMPK in mouse C2C12 cells assessed as increase in ACC phosphorylation at Ser79 residues at 1 mM after 1 hr by Western blot analysis 27887844
3T3L1 Function assay 2 mM 4 hrs Induction of AMPKalpha phosphorylation at Thr172 residue in mouse 3T3L1 cells at 2 mM after 4 hrs by Western blot analysis 29425817
C2C12 Function assay 0.2 mM 30 mins Inhibition of PTP1B in differentiated mouse C2C12 cells assessed as upregulation of ACC phosphorylation at Ser-79 residue at 0.2 mM after 30 mins by Western blot assay 28951079
RCC4 Function assay 1 mM 48 hrs Induction of autophagy in human RCC4 cells assessed as increase in LC3 conversion at 1 mM after 48 hrs by Western blot method 28325600
3T3L1 Function assay 0.2 mM Inhibition of adipogenesis in mouse 3T3L1 cells assessed as reduction in triglyceride content at 0.2 mM by colorimetric assay 26088335
3T3L1 Function assay 0.2 mM 3 days Reduction in SCD1 protein expression in mouse 3T3L1 cells at 0.2 mM after 3 days by Western blot method 26088335
3T3L1 Function assay 0.2 mM 3 days Reduction in SREBP-1c protein expression in mouse 3T3L1 cells at 0.2 mM after 3 days by Western blot method 26088335
3T3L1 Function assay 0.2 mM 9 days Activation of AMPK in mouse 3T3L1 cells assessed as increase in ACC Ser79 phosphorylation at 0.2 mM after 9 days by Western blot method 26088335
3T3L1 Function assay 0.2 mM 3 days Reduction in C/EBPalpha protein expression in mouse 3T3L1 cells at 0.2 mM after 3 days by Western blot method 26088335
3T3L1 Function assay 0.2 mM 3 days Reduction in PPARgamma protein expression in mouse 3T3L1 cells at 0.2 mM after 3 days by Western blot method 26088335
3T3L1 Function assay 0.2 mM 3 days Reduction in FAS protein expression in mouse 3T3L1 cells at 0.2 mM after 3 days by Western blot method 26088335
Klik om meer experimentele gegevens over cellijnen te bekijken

Chemische informatie, opslag en stabiliteit (Chemical Information, Storage & Stability)

Molecuulgewicht 258.23 Formule

C9H14N4O5

 Opslag (vanaf de datum van ontvangst)
CAS-nr. 2627-69-2 SDF downloaden Opslag van stamoplossingen

Synoniemen NSC105823, AICA Riboside Smiles C1=NC(=C(N1C2C(C(C(O2)CO)O)O)N)C(=O)N

Oplosbaarheid (Solubility)

In vitro
Batch:

DMSO : 51 mg/mL (197.49 mM)
(Met vocht verontreinigd DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Water : 20 mg/mL

Ethanol : Insoluble

Molariteitscalculator

Massa Concentratie Volume Molecuulgewicht
Verdunningscalculator Molecuulgewichtcalculator

In vivo
Batch:

In vivo formulatiecalculator (heldere oplossing)

Stap 1: Voer onderstaande informatie in (Aanbevolen: een extra dier om rekening te houden met verlies tijdens het experiment)

mg/kg g μL

Stap 2: Voer de in vivo formulering in (Dit is alleen de calculator, geen formulering. Neem eerst contact met ons op als er geen in vivo formulering is in de sectie oplosbaarheid.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Berekeningsresultaten:

Werkconcentratie: mg/ml;

Methode voor het bereiden van DMSO-moedervloeistof: mg geneesmiddel vooropgelost in μL DMSO ( Concentratie moedervloeistof mg/mL, Neem eerst contact met ons op als de concentratie de DMSO-oplosbaarheid van de batch van het geneesmiddel overschrijdt. )

Methode voor het bereiden van in vivo formulering: Neem μL DMSO moedervloeistof, voeg daarna toeμL PEG300, mengen en verhelderen, daarna toevoegenμL Tween 80, mengen en verhelderen, daarna toevoegen μL ddH2O, mengen en verhelderen.

Methode voor het bereiden van in vivo formulering: Neem μL DMSO moedervloeistof, voeg daarna toe μL Maïsolie, mengen en verhelderen.

Opmerking: 1. Zorg ervoor dat de vloeistof helder is voordat u het volgende oplosmiddel toevoegt.
2. Zorg ervoor dat u het/de oplosmiddel(en) in de juiste volgorde toevoegt. U moet ervoor zorgen dat de verkregen oplossing, bij de vorige toevoeging, een heldere oplossing is voordat u verdergaat met het toevoegen van het volgende oplosmiddel. Fysieke methoden zoals vortexen, ultrasoon of een warmwaterbad kunnen worden gebruikt om het oplossen te bevorderen.

Werkingsmechanisme (Mechanism of Action)

Kenmerken
A potential first-in-class ARA.
Targets/IC50/Ki
AMPK
(Cell-free assay)
AMPKK
(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. 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. 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 remarkedly reduces viability of B cells but not T cells. 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. AICAR causes a concentration-related reduction in CD18 expression on LPS-stimulated neutrophils in vitro. It 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. At 10 mg/kg, this compound results in higher fluid required to stabilize hemodynamics in pigs and inhibits LPS-induced protein permeability of pulmonary capillaries, peak inspiratory pressures on constant tidal volume and dead space ventilation.

Referenties
  • [4] https://pubmed.ncbi.nlm.nih.gov/8619186/
  • [5] https://pubmed.ncbi.nlm.nih.gov/7877305/

Toepassingen (Applications)

Methoden Biomarkers Afbeeldingen PMID
Western blot p-S6K1 / S6K1 / p-ERK / ERK p-IRS-1 / IRS-1 / p-AKT / AKT p-AMPK / p-ACC / p-eNOS / eNOS / vWF / VE-cadherin / ICAM-1 Cyclin D1 / p21 / p53
S1802-WB1
26528831
Immunofluorescence p-ERK YAZ / TAZ
S1802-IF1
26528831

Informatie over klinische proeven (Clinical Trial Information)

(gegevens van https://clinicaltrials.gov, bijgewerkt op 2016-11-08)

NCT-nummer Werving Aandoeningen Sponsor/medewerkers Startdatum Fasen
NCT01813838 TERMINATED
SMD
Groupe Francophone des Myelodysplasies
 2013-06 PHASE1; PHASE2
NCT00559624 COMPLETED
Leukemia, B-Cell, Chronic
Advancell - Advanced In Vitro Cell Technologies, S.A.
 2007-12 PHASE1; PHASE2
NCT00872001 TERMINATED
Coronary Artery Bypass; Myocardial Infarction; Ventricular Dysfunction, Left; Stroke; Cardiopulmonary Bypass
Merck Sharp & Dohme LLC
 2009-04 PHASE3
NCT00004314 COMPLETED
Lesch-Nyhan Syndrome
National Center for Research Resources (NCRR)
 1996-02 PHASE2
NCT00168519 COMPLETED
Diabetes Mellitus, Type 2
Baker Heart Research Institute
 2002-10