Acadesine

Identification

Logo pink
Are you a
new drug developer?
Contact us to learn more about our customized products and solutions.
Name
Acadesine
Accession Number
DB04944
Type
Small Molecule
Groups
Investigational
Description

Acadesine (AICA-riboside) is a purine nucleoside analog with anti-ischemic properties that is currently being studied (Phase 3) for the prevention of adverse cardiovascular outcomes in patients undergoing coronary artery bypass graft (CABG) surgery. It is being developed jointly by PeriCor and Schering-Plough. Acadesine has been granted Orphan Drug Designation for B-CLL in the EU.

Structure
Thumb
Synonyms
  • Acadesina
  • Acadesine
  • Acadesinum
  • AICA-riboside
External IDs
GP 1-110 / GP-1-110
International/Other Brands
Acadra
Categories
UNII
53IEF47846
CAS number
2627-69-2
Weight
Average: 258.2313
Monoisotopic: 258.096419578
Chemical Formula
C9H14N4O5
InChI Key
RTRQQBHATOEIAF-UUOKFMHZSA-N
InChI
InChI=1S/C9H14N4O5/c10-7-4(8(11)17)12-2-13(7)9-6(16)5(15)3(1-14)18-9/h2-3,5-6,9,14-16H,1,10H2,(H2,11,17)/t3-,5-,6-,9-/m1/s1
IUPAC Name
5-amino-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1H-imidazole-4-carboxamide
SMILES
[H][C@]1(CO)O[C@]([H])([C@H](O)[C@@H]1O)N1C=NC(C(N)=O)=C1N

Pharmacology

Indication

Investigated for use/treatment in cardiac reperfusion injury, cardiovascular disorders, and coronary artery disease.

Pharmacodynamics

Acadesine has been shown to induce cell death apoptosis selectively in B-cells taken from healthy subjects and patients with B-CLL, with little effect on T-cells. As T-cells have an important role in fighting infection, it is anticipated that patients treated with acadesine will have a reduced risk of serious infections compared to those on current chemotherapies.

Mechanism of action

The mechanism by which acadesine selectively kills B-cells is not yet fully elucidated. The action of acadesine does not require the tumour suppressor protein p53 like other treatments. This is important, as p53 is often missing or defective in cancerous B-cells. Studies have shown acadesine activates AMPK and induces apoptosis in B-cell chronic lymphocytic leukemia cells but not in T lymphocytes.

Absorption
Not Available
Volume of distribution
Not Available
Protein binding

Negligible (approximately 1%)

Metabolism
Not Available
Route of elimination
Not Available
Half life

1 week

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
Not Available

References

General References
  1. Dixon R, Fujitaki J, Sandoval T, Kisicki J: Acadesine (AICA-riboside): disposition and metabolism of an adenosine-regulating agent. J Clin Pharmacol. 1993 Oct;33(10):955-8. [PubMed:8227467]
  2. Menasche P, Jamieson WR, Flameng W, Davies MK: Acadesine: a new drug that may improve myocardial protection in coronary artery bypass grafting. Results of the first international multicenter study. Multinational Acadesine Study Group. J Thorac Cardiovasc Surg. 1995 Oct;110(4 Pt 1):1096-106. [PubMed:7475138]
  3. Nawarskas JJ: Acadesine: a unique cardioprotective agent for myocardial ischemia. Heart Dis. 1999 Sep-Oct;1(4):255-60. [PubMed:11720632]
  4. Campas C, Lopez JM, Santidrian AF, Barragan M, Bellosillo B, Colomer D, Gil J: Acadesine activates AMPK and induces apoptosis in B-cell chronic lymphocytic leukemia cells but not in T lymphocytes. Blood. 2003 May 1;101(9):3674-80. Epub 2003 Jan 9. [PubMed:12522004]
External Links
Human Metabolome Database
HMDB0062179
PubChem Compound
17513
PubChem Substance
175426912
ChemSpider
16560
ChEBI
28498
ChEMBL
CHEMBL1551724
Wikipedia
Acadesine
ATC Codes
C01EB13 — Acadesine

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1, 2CompletedTreatmentLeukemia, B-Cell, Chronic1
1, 2TerminatedTreatmentSMD1
3TerminatedPreventionCardiopulmonary Bypass / Coronary Artery Bypass Graft Surgery Patients / Myocardial Infarction / Strokes / Ventricular Dysfunction, Left1

Pharmacoeconomics

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

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)213 dec °CPhysProp
Predicted Properties
PropertyValueSource
Water Solubility25.0 mg/mLALOGPS
logP-1.8ALOGPS
logP-2.6ChemAxon
logS-1ALOGPS
pKa (Strongest Acidic)12.45ChemAxon
pKa (Strongest Basic)4.82ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area156.85 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity58.27 m3·mol-1ChemAxon
Polarizability24.03 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.8949
Blood Brain Barrier+0.9505
Caco-2 permeable-0.8296
P-glycoprotein substrateNon-substrate0.7398
P-glycoprotein inhibitor INon-inhibitor0.9548
P-glycoprotein inhibitor IINon-inhibitor0.9293
Renal organic cation transporterNon-inhibitor0.9573
CYP450 2C9 substrateNon-substrate0.8329
CYP450 2D6 substrateNon-substrate0.8498
CYP450 3A4 substrateNon-substrate0.6421
CYP450 1A2 substrateNon-inhibitor0.9295
CYP450 2C9 inhibitorNon-inhibitor0.9418
CYP450 2D6 inhibitorNon-inhibitor0.9527
CYP450 2C19 inhibitorNon-inhibitor0.9265
CYP450 3A4 inhibitorNon-inhibitor0.9582
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9793
Ames testNon AMES toxic0.9027
CarcinogenicityNon-carcinogens0.9076
BiodegradationNot ready biodegradable0.8589
Rat acute toxicity1.9372 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9975
hERG inhibition (predictor II)Non-inhibitor0.8938
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/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as imidazole ribonucleosides and ribonucleotides. These are organic compounds in which the C-1 of a ribosyl moiety is N-linked to an imidazole ring. Nucleotides have a phosphate group linked to the C5 carbon of the ribose (or deoxyribose) moiety. This class does not contain benzimidazole nucleosides and nucleotides.
Kingdom
Organic compounds
Super Class
Nucleosides, nucleotides, and analogues
Class
Imidazole ribonucleosides and ribonucleotides
Sub Class
Not Available
Direct Parent
Imidazole ribonucleosides and ribonucleotides
Alternative Parents
Glycosylamines / Pentoses / N-substituted imidazoles / Aminoimidazoles / Tetrahydrofurans / Heteroaromatic compounds / Secondary alcohols / Oxacyclic compounds / Carboximidic acids / Azacyclic compounds
show 4 more
Substituents
Imidazole ribonucleoside / Glycosyl compound / N-glycosyl compound / Pentose monosaccharide / Aminoimidazole / Monosaccharide / N-substituted imidazole / Azole / Heteroaromatic compound / Imidazole
show 18 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
nucleoside analogue, aminoimidazole, 1-ribosylimidazolecarboxamide (CHEBI:28498)

Drug created on October 21, 2007 16:23 / Updated on September 02, 2019 18:07