Acadesine (AICAR)

Names

[ Name ]:
Acadesine (AICAR)

[Synonym ]:
AIC-Riboside
EINECS 220-097-5
5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside
AICA Riboside
T5OTJ B1Q CQ DQ E- AT5N CNJ DVQ EZ &&Ribo-β-D Form
5-Amino-1-b-D-ribofuranosyl-1H-imidazole-4-carboxamide
Z-RIBOSIDE
5-Amino-4-imidazolecarboxamide ribonucleoside
5-Amino-1-(β-D-ribofuranosyl)-1H-imidazole-4-carboxamide
5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside
AICA-riboside
Imidazole-4-carboxamide, 5-amino-1-β-D-ribofuranosyl-
1H-Imidazole-4-carboxamide, 5-amino-1-β-D-ribofuranosyl-
GP 1-110
MFCD00869751
Acadesine
Arasine
AMPK
AICAR
5-Amino-1-β-ribofuranosyl-imidazole-4-carboxamide
5-Amino-1-beta-D-ribofuranosyl-1H-imidazole-4-carboxamide
5-amino-4-imidazole carboxamide ribonucleoside

Biological Activity

[Description]:

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

[Related Catalog]:

Signaling Pathways >> Epigenetics >> AMPK

Signaling Pathways >> PI3K/Akt/mTOR >> AMPK

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> Autophagy >> Mitophagy

Research Areas >> Cancer

[Target]

AMPK

Autophagy

Mitophagy

[In Vitro]

HepG2 cells are treated with various concentrations of AICAR (0.1-1.0 mM) for 12, 24, and 48 h, respectively. The expression level of IR-β significantly decreases with 0.25, 0.5, and 1.0 mM of AICAR at 48 h to 50%, 53%, and 46% of the control, respectively[1].

[In Vivo]

Fourteen-week-old male, lean (L; 31.3 g body wt) wild-type andob/ob (O; 59.6 g body wt) mice are injected with the AMP-activated kinase (AMPK) activator AICAR (A) at 0.5 mg/g per day or saline control (C) for 14 days. At 24 h after the last injection (including a 12-h fast), all mice are killed, and the plantar flexor complex muscle (gastrocnemius, soleus, and plantaris) is excised for analysis. Muscle mass is lower in OC (159±12 mg) than LC, LA, and OA (176±10, 178±9, and 166±16 mg, respectively) mice, independent of a body weight change[2]. The kidney weight is significantly higher in the untreated group when compared with both the exercise and AICAR (0.5 mg/g body wt) groups. The heart weight is higher in the exercise group than in the other groups, whereas the liver weight is significantly higher in the AICAR-treated group when compared with the exercise and untreated groups[3].

[Cell Assay]

HepG2 cells (5×105 cells) are plated in 6-well culture plate dishes and then are incubated in the serum-free media for 12 h before transfection. One microgram of plasmid is transfected with FuGENE6 Transfection Reagent. After 5 h of transfection, the culture media are removed and then media supplemented with or without AICAR (0.1-1.0 mM) are added to each well. The stimulation media are changed every 24 h[1].

[Animal admin]

Mice[2] Fourteen-week-old lean (Lepob/+ or Lepob/+) and ob/ob (Lepob/Lepob) male mice are uesd. After the 14-day experimental treatment (24 h after AICAR injection, including a 12-h fast), the plantar flexor complex muscle is cleanly (tendon-to-tendon) excised from an anesthetized mouse breathing 4% isoflurane. The muscle is quickly weighed and then processed for histology or frozen in liquid nitrogen and stored at −80°C. The anesthetized mice are killed by transection of the diaphragm and removal of the entire heart, after blood collection via needle puncture directly into the heart, while breathing 4% isoflurane. AICAR or saline (control) is injected subcutaneously into the lateral distal portion of the back. AICAR is administered at 0.5 mg/g per day one time for 14 days. Saline (control) is injected in volumes identical to those used for AICAR treatment in a manner identical to that of AICAR treatment. Body weight is measured prior to death. Rats[3] Male 5-week-old ZDF rats are either subcutaneously injected with a single dose of AICAR (0.5 mg/g body wt) or underwent a single bout of treadmill running (60 min, speed of 25 m/min at a 5% incline). Untreated ZDF rats serve as controls (n=5 in each group). One hour after the subcutaneous AICAR injection or immediately after treadmill running, rats are killed by cervical dislocation. To avoid any effect of muscle spasm and hypoxia, red and white gastrocnemius muscles are removed within seconds and immediately freeze clamped for later determination of AMPK activity.

[References]

[1]. Nakamaru K, et al. AICAR, an activator of AMP-activated protein kinase, down-regulates the insulin receptor expression in HepG2 cells. Biochem Biophys Res Commun. 2005 Mar 11;328(2):449-54

[2]. Drake JC, et al. AICAR treatment for 14 days normalizes obesity-induced dysregulation of TORC1 signaling and translational capacity in fasted skeletal muscle. Am J Physiol Regul Integr Comp Physiol. 2010 Dec;299(6):R1546-54.

[3]. Pold R, et al. Long-term AICAR administration and exercise prevents diabetes in ZDF rats.Diabetes. 2005 Apr;54(4):928-34.

[4]. Chen L, et al. Activating AMPK to Restore Tight Junction Assembly in Intestinal Epithelium and to Attenuate Experimental Colitis by Metformin. Front Pharmacol. 2018 Jul 16;9:761.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
2.1±0.1 g/cm3

[ Boiling Point ]:
726.3±60.0 °C at 760 mmHg

[ Melting Point ]:
214-215 °C

[ Molecular Formula ]:
C₉H₁₄N₄O₅

[ Molecular Weight ]:
258.231

[ Flash Point ]:
393.1±32.9 °C

[ Exact Mass ]:
258.096405

[ PSA ]:
156.85000

[ LogP ]:
-2.93

[ Vapour Pressure ]:
0.0±2.5 mmHg at 25°C

[ Index of Refraction ]:
1.821

[ Storage condition ]:
−20°C

[ Water Solubility ]:
H2O: >10 mg/mL

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H315-H319-H335

[ Precautionary Statements ]:
P261-P305 + P351 + P338

[ Personal Protective Equipment ]:
dust mask type N95 (US);Eyeshields;Gloves

[ Hazard Codes ]:
Xi: Irritant;

[ Risk Phrases ]:
R36/37/38

[ Safety Phrases ]:
S26-S36

[ RIDADR ]:
NONH for all modes of transport

[ WGK Germany ]:
3

[ HS Code ]:
2934999090

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2934999090

[ Summary ]:
2934999090. other heterocyclic compounds. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

Articles

Differential effects of AMPK agonists on cell growth and metabolism.

Oncogene 34 , 3627-39, (2015)

As a sensor of cellular energy status, the AMP-activated protein kinase (AMPK) is believed to act in opposition to the metabolic phenotypes favored by proliferating tumor cells. Consequently, compound...

Modulators of hepatic lipoprotein metabolism identified in a search for small-molecule inducers of tribbles pseudokinase 1 expression.

PLoS ONE 10 , e0120295, (2015)

Recent genome wide association studies have linked tribbles pseudokinase 1 (TRIB1) to the risk of coronary artery disease (CAD). Based on the observations that increased expression of TRIB1 reduces se...

Stimulatory Effects of Balanced Deep Sea Water on Mitochondrial Biogenesis and Function.

PLoS ONE 10 , e0129972, (2015)

The worldwide prevalence of metabolic diseases, including obesity and diabetes, is increasing. Mitochondrial dysfunction is recognized as a core feature of these diseases. Emerging evidence also sugge...

Related Compounds

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