Acadesine
Identification
- Generic Name
- Acadesine
- DrugBank Accession Number
- DB04944
- Background
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.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
- Weight
- Average: 258.2313
Monoisotopic: 258.096419578 - Chemical Formula
- C9H14N4O5
- Synonyms
- Acadesina
- Acadesine
- Acadesinum
- AICA-riboside
- External IDs
- GP 1-110
- GP-1-110
Pharmacology
- Indication
Investigated for use/treatment in cardiac reperfusion injury, cardiovascular disorders, and coronary artery disease.
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- 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
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Not Available
- 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
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- International/Other Brands
- Acadra
Categories
- ATC Codes
- C01EB13 — Acadesine
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- 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
- Alcohol / Amine / Aminoimidazole / Aromatic heteromonocyclic compound / Azacycle / Azole / Carboximidic acid / Carboximidic acid derivative / Glycosyl compound / Heteroaromatic compound show 18 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- nucleoside analogue, aminoimidazole, 1-ribosylimidazolecarboxamide (CHEBI:28498)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 53IEF47846
- CAS number
- 2627-69-2
- 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
References
- General References
- 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. [Article]
- 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. [Article]
- Nawarskas JJ: Acadesine: a unique cardioprotective agent for myocardial ischemia. Heart Dis. 1999 Sep-Oct;1(4):255-60. [Article]
- 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. [Article]
- External Links
- Human Metabolome Database
- HMDB0062179
- PubChem Compound
- 17513
- PubChem Substance
- 175426912
- ChemSpider
- 16560
- ChEBI
- 28498
- ChEMBL
- CHEMBL1551724
- ZINC
- ZINC000003798074
- Wikipedia
- Acadesine
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 3 Terminated Prevention Cardiopulmonary Bypass / Coronary Artery Bypass Grafting (CABG) / Left Ventricular Dysfunction / Myocardial Infarction / Stroke 1 1, 2 Completed Treatment Leukemia, B-Cell, Chronic 1 1, 2 Terminated Treatment SMD 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 213 dec °C PhysProp - Predicted Properties
Property Value Source Water Solubility 25.0 mg/mL ALOGPS logP -1.8 ALOGPS logP -2.6 Chemaxon logS -1 ALOGPS pKa (Strongest Acidic) 12.45 Chemaxon pKa (Strongest Basic) 4.82 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 7 Chemaxon Hydrogen Donor Count 5 Chemaxon Polar Surface Area 156.85 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 58.27 m3·mol-1 Chemaxon Polarizability 24.03 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.8949 Blood Brain Barrier + 0.9505 Caco-2 permeable - 0.8296 P-glycoprotein substrate Non-substrate 0.7398 P-glycoprotein inhibitor I Non-inhibitor 0.9548 P-glycoprotein inhibitor II Non-inhibitor 0.9293 Renal organic cation transporter Non-inhibitor 0.9573 CYP450 2C9 substrate Non-substrate 0.8329 CYP450 2D6 substrate Non-substrate 0.8498 CYP450 3A4 substrate Non-substrate 0.6421 CYP450 1A2 substrate Non-inhibitor 0.9295 CYP450 2C9 inhibitor Non-inhibitor 0.9418 CYP450 2D6 inhibitor Non-inhibitor 0.9527 CYP450 2C19 inhibitor Non-inhibitor 0.9265 CYP450 3A4 inhibitor Non-inhibitor 0.9582 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9793 Ames test Non AMES toxic 0.9027 Carcinogenicity Non-carcinogens 0.9076 Biodegradation Not ready biodegradable 0.8589 Rat acute toxicity 1.9372 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9975 hERG inhibition (predictor II) Non-inhibitor 0.8938
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-0596-9430000000-675bbf40b4a04dfec20f Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-08fr-0910000000-20b3b227f602b630be09 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0a6r-1920000000-14ed366edeedad6f2b58 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-08ir-1910000000-ab4f18a20000bf36b038 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0a4i-4900000000-6770a2bec7f29abe6f70 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0a6r-1900000000-20c44dddd7e710686637 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0006-9500000000-1a98ed626a31ea648386 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 166.388084 predictedDarkChem Lite v0.1.0 [M-H]- 167.579284 predictedDarkChem Lite v0.1.0 [M-H]- 154.13832 predictedDeepCCS 1.0 (2019) [M+H]+ 166.199084 predictedDarkChem Lite v0.1.0 [M+H]+ 168.569684 predictedDarkChem Lite v0.1.0 [M+H]+ 156.49992 predictedDeepCCS 1.0 (2019) [M+Na]+ 165.943084 predictedDarkChem Lite v0.1.0 [M+Na]+ 167.948884 predictedDarkChem Lite v0.1.0 [M+Na]+ 164.01598 predictedDeepCCS 1.0 (2019)
Drug created at October 21, 2007 22:23 / Updated at January 14, 2023 19:03