Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C9H15N4O8P |
Molecular Weight | 338.2112 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 4 / 4 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
NC(=O)C1=C(N)N(C=N1)[C@@H]2O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]2O
InChI
InChIKey=NOTGFIUVDGNKRI-UUOKFMHZSA-N
InChI=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
AICAR (Acadesine) is an intermediate in the generation of inosine monophosphate. AICAR is an analog of adenosine monophosphate (AMP) that is capable of stimulating AMP-dependent protein kinase (AMPK) activity. AICAR has been used clinically to treat and protect against cardiac ischemic injury. The drug was first used in the 1980s as a method to preserve blood flow to the heart during surgery. The drug has also been shown as a potential treatment for diabetes by increasing the metabolic activity of tissues by changing the physical composition of muscle. Acadesine is an adenosine receptor agonist (ARA) in development for the treatment of ischaemia-reperfusion injury and chronic lymphocytic leukaemia. Schering-Plough is developing the compound as a cardioprotective agent in ischaemia-reperfusion injury. Avancell and Protherics are co-developing acadesine for the treatment of B-cell chronic lymphocytic leukaemia (B-CLL). Clinical development is underway for both indications. AICAR, an AMPK activator, results in accumulation of ZMP, which mimics the stimulating effect of AMP on AMPK and AMPK kinase. Orphan drug status has been granted for acadesine in the EU for the treatment of B-cell chronic lymphocytic leukaemia.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
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Target ID: CHEMBL2096907 |
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380.0 µM [EC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Preventing | Unknown Approved UseUnknown |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
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Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
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no [IC50 26.6032 uM] | ||||
no | ||||
no | ||||
no | ||||
Sources: https://pubmed.ncbi.nlm.nih.gov/21205922/ |
no | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/21205922/ |
no | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/21205922/ |
no | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/21205922/ |
no | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/21205922/ |
yes | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/21205922/ |
yes |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
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Acadesine (AICA-riboside): disposition and metabolism of an adenosine-regulating agent. | 1993 Oct |
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5-aminoimidazole-4-carboxamide ribonucleoside. A specific method for activating AMP-activated protein kinase in intact cells? | 1995 Apr 15 |
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AICA riboside increases AMP-activated protein kinase, fatty acid oxidation, and glucose uptake in rat muscle. | 1997 Dec |
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The protective effect of acadesine on lung ischemia-reperfusion injury. | 2001 Mar |
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Targeting the AMP-activated protein kinase for the treatment of type 2 diabetes. | 2002 Jul |
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Protein kinase inhibitors block the stimulation of the AMP-activated protein kinase by 5-amino-4-imidazolecarboxamide riboside. | 2002 Nov 6 |
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AMP-activated protein kinase can induce apoptosis of insulin-producing MIN6 cells through stimulation of c-Jun-N-terminal kinase. | 2003 Apr |
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Acadesine activates AMPK and induces apoptosis in B-cell chronic lymphocytic leukemia cells but not in T lymphocytes. | 2003 May 1 |
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AMP-activated protein kinase: the guardian of cardiac energy status. | 2004 Aug |
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AICA riboside both activates AMP-activated protein kinase and competes with adenosine for the nucleoside transporter in the CA1 region of the rat hippocampus. | 2004 Mar |
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Intracerebroventricular infusion of glucose, insulin, and the adenosine monophosphate-activated kinase activator, 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside, controls muscle glycogen synthesis. | 2004 Sep |
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Acadesine induces apoptosis in B cells from mantle cell lymphoma and splenic marginal zone lymphoma. | 2005 Feb |
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5-aminoimidazole-4-carboxamide riboside (AICAR) enhances GLUT2-dependent jejunal glucose transport: a possible role for AMPK. | 2005 Jan 15 |
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Anti-lipolytic action of AMP-activated protein kinase in rodent adipocytes. | 2005 Jul 1 |
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Enhanced insulin-stimulated glycogen synthesis in response to insulin, metformin or rosiglitazone is associated with increased mRNA expression of GLUT4 and peroxisomal proliferator activator receptor gamma co-activator 1. | 2005 Jun |
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5-amino-imidazole carboxamide riboside acutely potentiates glucose-stimulated insulin secretion from mouse pancreatic islets by KATP channel-dependent and -independent pathways. | 2005 May 20 |
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Analysis of intracellular nucleotides by capillary electrophoresis-mass spectrometry. | 2006 |
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AMPK or ZMPK? | 2006 |
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A3 adenosine receptors and mitogen-activated protein kinases in lung injury following in vivo reperfusion. | 2006 |
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Moving preconditioning from bench to bedside. | 2006 Jul 4 |
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Adiponectin suppression of high-glucose-induced reactive oxygen species in vascular endothelial cells: evidence for involvement of a cAMP signaling pathway. | 2006 Jun |
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Diagnosing AICA-ribosiduria by capillary electrophoresis. | 2006 Oct 20 |
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Ischemic preconditioning: protection against myocardial necrosis and apoptosis. | 2007 |
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Covariate heterogeneity in meta-analysis: criteria for deciding between meta-regression and individual patient data. | 2007 Jul 10 |
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5-Aminoimidazole-4-carboxamide riboside sensitizes TRAIL- and TNF{alpha}-induced cytotoxicity in colon cancer cells through AMP-activated protein kinase signaling. | 2007 May |
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Acadesine: AICA riboside, ARA 100, arasine, GP 1 110. | 2008 |
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The need for a multi-level biochemical approach to defeat cancer that will also support the host. | 2008 Oct |
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AMP-activated protein kinase pathway: a potential therapeutic target in cardiometabolic disease. | 2009 Apr |
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AICAR activates the pluripotency transcriptional network in embryonic stem cells and induces KLF4 and KLF2 expression in fibroblasts. | 2009 Feb 12 |
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Kinase activity-independent suppression of p73alpha by AMP-activated kinase alpha (AMPKalpha). | 2009 Feb 19 |
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Beyond AICA riboside: in search of new specific AMP-activated protein kinase activators. | 2009 Jan |
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Gateways to clinical trials. | 2009 Mar |
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Blunting of AICAR-induced human skeletal muscle glucose uptake in type 2 diabetes is dependent on age rather than diabetic status. | 2009 May |
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AMP-activated protein kinase enhances the expression of muscle-specific ubiquitin ligases despite its activation of IGF-1/Akt signaling in C2C12 myotubes. | 2009 Oct 1 |
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Germline deletion of AMP-activated protein kinase beta subunits reduces bone mass without altering osteoclast differentiation or function. | 2010 Jan |
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Whole blood transcriptomics in cardiac surgery identifies a gene regulatory network connecting ischemia reperfusion with systemic inflammation. | 2010 Oct 27 |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT00872001
AICAR (Acadesine) 42 mg/kg diluted in normal saline to a total of 500 mL, delivered as an IV infusion over approximately 7 hours commencing within approximately 30 minutes before induction of anesthesia at a rate of 0.1 mg/kg/min (translating into 1.2 mL/min for a 500 mL solution). In addition, a 5 µg/mL cardioplegia solution of acadesine will be administered, and acadesine will be added to the priming solution (5 µg/mL) in the heart lung machine during CPB.
Route of Administration:
Intravenous
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/7744080
AICAR (Acadesine) (500 uM) 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 uM) 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 uM) causes a dramatic inhibition of both fatty acid and sterol synthesis in rat hepatocytes. Acadesine (500 uM) also causes a dramatic inactivation of HMG-CoA reductase.
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3031-94-5
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18406
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AICA RIBONUCLEOTIDE
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65110
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SUBSTANCE RECORD