AICA ribonucleotide

Identification

Name
AICA ribonucleotide
Accession Number
DB01700  (EXPT00407)
Type
Small Molecule
Groups
Experimental, Investigational
Description

5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR) 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. Currently, 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.

Structure
Thumb
Synonyms
  • 1-(5'-phosphoribosyl)-5-amino-4-imidazolecarboxamide
  • 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide
  • 5-aminoimidazole-4-carboxamide ribotide
  • 5-phosphoribosyl-4-carbamoyl-5-aminoimidazole
  • 5'-phospho-ribosyl-5-amino-4-imidazole carboxamide
  • 5'-phosphoribosyl-5-amino-4-imidazolecarboxamide
  • acadesine 5'-monophosphate
  • AICA-ribonucleotide
  • AICAR
Categories
UNII
F0X88YW0YK
CAS number
3031-94-5
Weight
Average: 338.2112
Monoisotopic: 338.062749988
Chemical Formula
C9H15N4O8P
InChI Key
NOTGFIUVDGNKRI-UUOKFMHZSA-N
InChI
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
IUPAC Name
{[(2R,3S,4R,5R)-5-(5-amino-4-carbamoyl-1H-imidazol-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}phosphonic acid
SMILES
NC(=O)C1=C(N)N(C=N1)[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O

Pharmacology

Indication
Not Available
Pharmacodynamics
Not Available
Mechanism of action
TargetActionsOrganism
UBifunctional purine biosynthesis protein PURHNot AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
PathwayCategory
Lesch-Nyhan Syndrome (LNS)Disease
Myoadenylate deaminase deficiencyDisease
Adenosine Deaminase DeficiencyDisease
Molybdenum Cofactor DeficiencyDisease
Xanthinuria type IDisease
Xanthinuria type IIDisease
Purine Nucleotides De Novo Biosynthesis 2Metabolic
Purine MetabolismMetabolic
Adenosine Deaminase DeficiencyDisease
Xanthine Dehydrogenase Deficiency (Xanthinuria)Disease
purine nucleotides de novo biosynthesis Metabolic
Thioguanine Action PathwayDrug action
Histidine BiosynthesisMetabolic
Histidine MetabolismMetabolic
Purine MetabolismMetabolic
Adenylosuccinate Lyase DeficiencyDisease
Molybdenum Cofactor DeficiencyDisease
Purine Nucleoside Phosphorylase DeficiencyDisease
Adenine phosphoribosyltransferase deficiency (APRT)Disease
Mitochondrial DNA depletion syndromeDisease
Purine MetabolismMetabolic
AICA-RibosiduriaDisease
Xanthine Dehydrogenase Deficiency (Xanthinuria)Disease
Azathioprine Action PathwayDrug action
Gout or Kelley-Seegmiller SyndromeDisease
Azathioprine Action PathwayDrug action
Xanthinuria type IIDisease
purine nucleotides de novo biosynthesisMetabolic
Histidine BiosynthesisMetabolic
Purine MetabolismMetabolic
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
Acetylsalicylic acidAcetylsalicylic acid may increase the hypoglycemic activities of AICA ribonucleotide.
AmcinonideThe therapeutic efficacy of AICA ribonucleotide can be decreased when used in combination with Amcinonide.
Aminosalicylic AcidAminosalicylic Acid may increase the hypoglycemic activities of AICA ribonucleotide.
AmitriptylineAmitriptyline may decrease the hypoglycemic activities of AICA ribonucleotide.
AripiprazoleThe therapeutic efficacy of AICA ribonucleotide can be decreased when used in combination with Aripiprazole.
Arsenic trioxideThe therapeutic efficacy of AICA ribonucleotide can be decreased when used in combination with Arsenic trioxide.
ArticaineThe therapeutic efficacy of AICA ribonucleotide can be decreased when used in combination with Articaine.
AsenapineThe therapeutic efficacy of AICA ribonucleotide can be decreased when used in combination with Asenapine.
AtazanavirThe therapeutic efficacy of AICA ribonucleotide can be decreased when used in combination with Atazanavir.
BendroflumethiazideThe therapeutic efficacy of AICA ribonucleotide can be decreased when used in combination with Bendroflumethiazide.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0001517
KEGG Compound
C04677
PubChem Compound
65110
PubChem Substance
46508570
ChemSpider
58620
BindingDB
22579
ChEBI
18406
ChEMBL
CHEMBL483849
HET
AMZ
Wikipedia
AICA_ribonucleotide
PDB Entries
1m9n / 1p4r / 1pl0 / 2cnq / 2ntl / 2qre / 2r7k / 2r7l / 2r84 / 2uv5
show 10 more

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
Not AvailableCompletedTreatmentType 2 Diabetes Mellitus1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility2.79 mg/mLALOGPS
logP-2.2ALOGPS
logP-4.8ChemAxon
logS-2.1ALOGPS
pKa (Strongest Acidic)1.22ChemAxon
pKa (Strongest Basic)4.8ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count9ChemAxon
Hydrogen Donor Count6ChemAxon
Polar Surface Area203.38 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity69.14 m3·mol-1ChemAxon
Polarizability28.57 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.903
Blood Brain Barrier+0.9226
Caco-2 permeable-0.7239
P-glycoprotein substrateNon-substrate0.7073
P-glycoprotein inhibitor INon-inhibitor0.8892
P-glycoprotein inhibitor IINon-inhibitor0.9716
Renal organic cation transporterNon-inhibitor0.9664
CYP450 2C9 substrateNon-substrate0.8032
CYP450 2D6 substrateNon-substrate0.8426
CYP450 3A4 substrateNon-substrate0.6249
CYP450 1A2 substrateNon-inhibitor0.8664
CYP450 2C9 inhibitorNon-inhibitor0.9028
CYP450 2D6 inhibitorNon-inhibitor0.9083
CYP450 2C19 inhibitorNon-inhibitor0.8902
CYP450 3A4 inhibitorNon-inhibitor0.9368
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.985
Ames testNon AMES toxic0.8452
CarcinogenicityNon-carcinogens0.8999
BiodegradationNot ready biodegradable0.8328
Rat acute toxicity2.4155 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9938
hERG inhibition (predictor II)Non-inhibitor0.8014
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-004i-0914000000-84c17cba09b2fb11b4d1
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-01t9-1900000000-ebd6a0aeccf60882a9c4
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-056r-7900000000-674e1cf6f4488a373690
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-004r-9617000000-715abdd95d031de269f0
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-9400000000-f3a4c70c454a0da6eb32
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-9000000000-3019a28f446b6ae4ee1f
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-000i-0009000000-7425edce1492dba01a40
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-000i-1019000000-4ca07d05181423b32ed1
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-004j-9300000000-5c28ca5957750fa338e3
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-004i-9200000000-70e563a806a4c3a55e97
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-004i-9100000000-74be45171db0b5560214
LC-MS/MS Spectrum - LC-ESI-QTOF , negativeLC-MS/MSsplash10-004r-9104000000-230fd9fc88d41766b56e
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-000i-0119000000-9504e432c77e845f195d
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-056r-1921000000-b59f42e588be20adfd16
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-03di-2900000000-4725adb433c2ef4f7e01
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-03di-4900000000-731f94a980a3ea830720
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-03di-5900000000-e2c302b537e2a87761ca
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-03di-2900000000-f0dad518d8c8a1fa40e2

Taxonomy

Description
This compound belongs to the class of organic compounds known as 1-ribosyl-imidazolecarboxamides. These are organic compounds containing the imidazole ring linked to a ribose ring through a 1-2 bond.
Kingdom
Organic compounds
Super Class
Nucleosides, nucleotides, and analogues
Class
Imidazole ribonucleosides and ribonucleotides
Sub Class
1-ribosyl-imidazolecarboxamides
Direct Parent
1-ribosyl-imidazolecarboxamides
Alternative Parents
Pentose phosphates / Glycosylamines / Monosaccharide phosphates / 2-heteroaryl carboxamides / Monoalkyl phosphates / Carbonylimidazoles / Aminoimidazoles / N-substituted imidazoles / Tetrahydrofurans / Heteroaromatic compounds
show 11 more
Substituents
1-ribosyl-imidazolecarboxamide / Pentose phosphate / Pentose-5-phosphate / Glycosyl compound / N-glycosyl compound / Monosaccharide phosphate / Pentose monosaccharide / 2-heteroaryl carboxamide / Imidazole-4-carbonyl group / Monoalkyl phosphate
show 31 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
1-(phosphoribosyl)imidazolecarboxamide, aminoimidazole (CHEBI:18406)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Protein homodimerization activity
Specific Function
Bifunctional enzyme that catalyzes 2 steps in purine biosynthesis.Promotes insulin receptor/INSR autophosphorylation and is involved in INSR internalization (PubMed:25687571).
Gene Name
ATIC
Uniprot ID
P31939
Uniprot Name
Bifunctional purine biosynthesis protein PURH
Molecular Weight
64615.255 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]

Drug created on June 13, 2005 07:24 / Updated on August 02, 2018 04:40