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Record Information
Version2.0
Creation Date2014-09-11 02:04:30 UTC
Update Date2014-12-24 20:26:55 UTC
Accession NumberT3D4677
Identification
Common NameAzathioprine
ClassSmall Molecule
DescriptionAzathioprine is only found in individuals that have used or taken this drug. It is an immunosuppressive pro-drug. It is converted into 6-mercaptopurine in the body where it blocks purine metabolism and DNA synthesis.Azathioprine antagonizes purine metabolism and may inhibit synthesis of DNA, RNA, and proteins. It may also interfere with cellular metabolism and inhibit mitosis. Its mechanism of action is likely due to incorporation of thiopurine analogues into the DNA structure, causing chain termination and cytotoxicity.
Compound Type
  • Antimetabolite
  • Antimetabolite, Antineoplastic
  • Antirheumatic Agent
  • Drug
  • Ether
  • Immunosuppressive Agent
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
6-((1-Methyl-4-nitro-1H-imidazol-5-yl)thio)-1H-purine
6-(1'-Methyl-4'-nitro-5'-imidazolyl)-mercaptopurine
Azamun
Azanin
Azasan
Azathioprin
Azatioprin
Azothioprine
Imuran
Imurek
Imurel
Chemical FormulaC9H7N7O2S
Average Molecular Mass277.263 g/mol
Monoisotopic Mass277.038 g/mol
CAS Registry Number446-86-6
IUPAC Name6-[(1-methyl-4-nitro-1H-imidazol-5-yl)sulfanyl]-7H-purine
Traditional Nameazathioprine
SMILESCN1C=NC(=C1SC1=NC=NC2=C1N=CN2)N(=O)=O
InChI IdentifierInChI=1S/C9H7N7O2S/c1-15-4-14-7(16(17)18)9(15)19-8-5-6(11-2-10-5)12-3-13-8/h2-4H,1H3,(H,10,11,12,13)
InChI KeyInChIKey=LMEKQMALGUDUQG-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as diarylthioethers. These are organosulfur compounds containing a thioether group that is substituted by two aryl groups.
KingdomOrganic compounds
Super ClassOrganosulfur compounds
ClassThioethers
Sub ClassAryl thioethers
Direct ParentDiarylthioethers
Alternative Parents
Substituents
  • Diarylthioether
  • 6-thiopurine
  • Imidazopyrimidine
  • Purine
  • Nitroaromatic compound
  • Nitroimidazole
  • N-substituted imidazole
  • Imidolactam
  • Pyrimidine
  • Azole
  • Imidazole
  • Heteroaromatic compound
  • C-nitro compound
  • Organic nitro compound
  • Azacycle
  • Organic oxoazanium
  • Organoheterocyclic compound
  • Organic 1,3-dipolar compound
  • Sulfenyl compound
  • Propargyl-type 1,3-dipolar organic compound
  • Allyl-type 1,3-dipolar organic compound
  • Organic nitrogen compound
  • Organonitrogen compound
  • Organic oxygen compound
  • Organopnictogen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organic zwitterion
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point243.5°C
Boiling PointNot Available
Solubility1.07e+00 g/L
LogP0.1
Predicted Properties
PropertyValueSource
Water Solubility1.07 g/LALOGPS
logP0.84ALOGPS
logP1.17ChemAxon
logS-2.4ALOGPS
pKa (Strongest Acidic)8.65ChemAxon
pKa (Strongest Basic)4ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area118.1 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity70.95 m³·mol⁻¹ChemAxon
Polarizability24.26 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-004i-9680000000-14a922ede69208f7d93dJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableJSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-001l-2950000000-4d3fb67844876c217814JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-000x-0950000000-b6de6073310270167ffbJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-004i-0390000000-0d11d23373539cfb283cJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-000x-0950000000-b6de6073310270167ffbJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-001l-2950000000-4d3fb67844876c217814JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 35V, Negativesplash10-004i-0390000000-58368875ea6ed88ee61cJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 15V, Negativesplash10-004i-0090000000-21d13daccc3ca6311829JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 30V, Negativesplash10-004i-0590000000-b73f9f2e26259b004f75JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 90V, Positivesplash10-01b9-7900000000-b14a64aca199c8b71cafJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 75V, Positivesplash10-0gir-6910000000-5e2cea2a00375e82d294JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 15V, Positivesplash10-0006-0950000000-dd45895b2d199860f157JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 30V, Positivesplash10-000x-2950000000-f4883419404f23b8f2a1JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 60V, Positivesplash10-0gir-5920000000-c941e300fe4d1869fd8eJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 45V, Positivesplash10-00lv-4930000000-c315bdc3abb371f4e426JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 60V, Positivesplash10-0gir-5920000000-3d187b69fbd90dc9b4deJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 90V, Positivesplash10-01b9-7900000000-c328e8adab736ddf2819JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 60V, Negativesplash10-0a4i-0900000000-b07a1492f0de60ac50ceJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 90V, Negativesplash10-07vl-4900000000-3773c3f34878b3d9eef8JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 75V, Negativesplash10-0aor-2900000000-aa84765db89a7c5cac3dJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-004i-0090000000-127672e50f7d85ca7302JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-05i0-0090000000-7bb3b92e927e16854e1dJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4i-9120000000-e50a6491ae4f28b8eeb0JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-3090000000-df6cb72af7b792b5cdfbJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-004i-2490000000-b8ce493eef32ac50f458JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00ba-5910000000-2134d4c288ab79f6a689JSpectraViewer
Toxicity Profile
Route of ExposureWell absorbed following oral administration.
Mechanism of ToxicityAzathioprine antagonizes purine metabolism and may inhibit synthesis of DNA, RNA, and proteins. It may also interfere with cellular metabolism and inhibit mitosis. Its mechanism of action is likely due to incorporation of thiopurine analogues into the DNA structure, causing chain termination and cytotoxicity.
MetabolismPrimarily converted to the active metabolites 6-mercaptopurine and 6-thioinosinic acid via a non-enzymatica process and glutathione transferases. Activation of 6-mercaptopurine occurs via hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and a series of multi-enzymatic processes involving kinases to form 6-thioguanine nucleotides (6-TGNs) as major metabolites Route of Elimination: Both compounds are rapidly eliminated from blood and are oxidized or methylated in erythrocytes and liver; no azathioprine or mercaptopurine is detectable in urine after 8 hours.
Toxicity ValuesThe oral LD50 for single doses of azathioprine in mice and rats are 2500 mg/kg and 400 mg/kg, respectively.
Lethal DoseNot Available
Carcinogenicity (IARC Classification)1, carcinogenic to humans. (4)
Uses/SourcesAzathioprine is used alone or in combination with other immunosuppressive therapy to prevent rejection following organ transplantation, and to treat an array of autoimmune diseases, including rheumatoid arthritis, pemphigus, systemic lupus erythematosus, Behcet's disease and other forms of vasculitis, autoimmune hepatitis, atopic dermatitis, myasthenia gravis, neuromyelitis optica (Devic's disease), restrictive lung disease, and others. It is also an important therapy and steroid-sparing agent for inflammatory bowel disease (such as Crohn's disease and ulcerative colitis) and for multiple sclerosis. In the United States it is currently approved by the Food and Drug Administration (FDA) for use in kidney transplantation from human donors, and for rheumatoid arthritis. Other uses are off-label. (Wikipedia)
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00993
HMDB IDHMDB15128
PubChem Compound ID2265
ChEMBL IDCHEMBL1542
ChemSpider ID2178
KEGG IDC06837
UniProt IDNot Available
OMIM ID
ChEBI ID2948
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkAzathioprine
References
Synthesis ReferenceNot Available
MSDSLink
General References
  1. Konstantopoulou M, Belgi A, Griffiths KD, Seale JR, Macfarlane AW: Azathioprine-induced pancytopenia in a patient with pompholyx and deficiency of erythrocyte thiopurine methyltransferase. BMJ. 2005 Feb 12;330(7487):350-1. [15705694 ]
  2. Woodroffe R, Yao GL, Meads C, Bayliss S, Ready A, Raftery J, Taylor RS: Clinical and cost-effectiveness of newer immunosuppressive regimens in renal transplantation: a systematic review and modelling study. Health Technol Assess. 2005 May;9(21):1-179, iii-iv. [15899149 ]
  3. Gombar VK, Enslein K, Blake BW: Carcinogenicity of azathioprine: an S-AR investigation. Mutat Res. 1993 May;302(1):7-12. [7683109 ]
  4. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Protein homodimerization activity
Specific Function:
Converts guanine to guanosine monophosphate, and hypoxanthine to inosine monophosphate. Transfers the 5-phosphoribosyl group from 5-phosphoribosylpyrophosphate onto the purine. Plays a central role in the generation of purine nucleotides through the purine salvage pathway.
Gene Name:
HPRT1
Uniprot ID:
P00492
Molecular Weight:
24579.155 Da
References
  1. Anstey A, Lear JT: Azathioprine: clinical pharmacology and current indications in autoimmune disorders. BioDrugs. 1998 Jan;9(1):33-47. [18020555 ]
  2. Dubinsky MC: Azathioprine, 6-mercaptopurine in inflammatory bowel disease: pharmacology, efficacy, and safety. Clin Gastroenterol Hepatol. 2004 Sep;2(9):731-43. [15354273 ]