Azathioprine (CHEM003635)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesTargets (3)XML
Record Information
Version1.0
Creation Date2014-09-11 02:04:30 UTC
Update Date2026-05-14 16:55:13 UTC
Accession NumberCHEM003635
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.
Contaminant Sources
  • HMDB Contaminants - Urine
  • IARC Carcinogens Group 1
  • STOFF IDENT Compounds
  • T3DB toxins
  • ToxCast & Tox21 Chemicals
Contaminant Type
  • Antimetabolite
  • Antimetabolite, Antineoplastic
  • Antirheumatic Agent
  • Drug
  • Ether
  • Human Neurotoxin
  • Immunosuppressive Agent
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
ValueSource
6-((1-Methyl-4-nitro-1H-imidazol-5-yl)thio)-1H-purineChEBI
6-(1'-Methyl-4'-nitro-5'-imidazolyl)-mercaptopurineChEBI
ImuranChEBI
AzasanKegg
AzathioprinHMDB
AzatioprinHMDB
AzothioprineHMDB
Azathioprine sodium saltHMDB
Azathioprine sodiumHMDB
Azathioprine sulfateHMDB
ImmuranHMDB
ImurelHMDB
Sodium, azathioprineHMDB
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=C1NC=N2)[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 KeyLMEKQMALGUDUQG-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
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 RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-004i-9680000000-14a922ede69208f7d93dSpectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-001l-2950000000-4d3fb67844876c217814Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-000x-0950000000-b6de6073310270167ffbSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-004i-0390000000-0d11d23373539cfb283cSpectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-000x-0950000000-b6de6073310270167ffbSpectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-001l-2950000000-4d3fb67844876c217814Spectrum
LC-MS/MSLC-MS/MS Spectrum - 35V, Negativesplash10-004i-0390000000-58368875ea6ed88ee61cSpectrum
LC-MS/MSLC-MS/MS Spectrum - 15V, Negativesplash10-004i-0090000000-21d13daccc3ca6311829Spectrum
LC-MS/MSLC-MS/MS Spectrum - 30V, Negativesplash10-004i-0590000000-b73f9f2e26259b004f75Spectrum
LC-MS/MSLC-MS/MS Spectrum - 90V, Positivesplash10-01b9-7900000000-b14a64aca199c8b71cafSpectrum
LC-MS/MSLC-MS/MS Spectrum - 75V, Positivesplash10-0gir-6910000000-5e2cea2a00375e82d294Spectrum
LC-MS/MSLC-MS/MS Spectrum - 15V, Positivesplash10-0006-0950000000-dd45895b2d199860f157Spectrum
LC-MS/MSLC-MS/MS Spectrum - 30V, Positivesplash10-000x-2950000000-f4883419404f23b8f2a1Spectrum
LC-MS/MSLC-MS/MS Spectrum - 60V, Positivesplash10-0gir-5920000000-c941e300fe4d1869fd8eSpectrum
LC-MS/MSLC-MS/MS Spectrum - 45V, Positivesplash10-00lv-4930000000-c315bdc3abb371f4e426Spectrum
LC-MS/MSLC-MS/MS Spectrum - 60V, Positivesplash10-0gir-5920000000-3d187b69fbd90dc9b4deSpectrum
LC-MS/MSLC-MS/MS Spectrum - 90V, Positivesplash10-01b9-7900000000-c328e8adab736ddf2819Spectrum
LC-MS/MSLC-MS/MS Spectrum - 60V, Negativesplash10-0a4i-0900000000-b07a1492f0de60ac50ceSpectrum
LC-MS/MSLC-MS/MS Spectrum - 90V, Negativesplash10-07vl-4900000000-3773c3f34878b3d9eef8Spectrum
LC-MS/MSLC-MS/MS Spectrum - 75V, Negativesplash10-0aor-2900000000-aa84765db89a7c5cac3dSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-004i-0090000000-127672e50f7d85ca7302Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-05i0-0090000000-7bb3b92e927e16854e1dSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4i-9120000000-e50a6491ae4f28b8eeb0Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-3090000000-df6cb72af7b792b5cdfbSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-004i-2490000000-b8ce493eef32ac50f458Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00ba-5910000000-2134d4c288ab79f6a689Spectrum
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
Concentrations
Not Available
DrugBank IDDB00993
HMDB IDHMDB0015128
FooDB IDNot Available
Phenol Explorer IDNot Available
KNApSAcK IDNot Available
BiGG IDNot Available
BioCyc IDNot Available
METLIN IDNot Available
PDB IDNot Available
Wikipedia LinkAzathioprine
Chemspider ID2178
ChEBI ID2948
PubChem Compound ID2265
Kegg Compound IDC06837
YMDB IDNot Available
ECMDB IDNot Available
References
Synthesis ReferenceNot Available
MSDSLink
General References
1. Gombar VK, Enslein K, Blake BW: Carcinogenicity of azathioprine: an S-AR investigation. Mutat Res. 1993 May;302(1):7-12.
2. 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.
3. 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.
4. https://www.ncbi.nlm.nih.gov/pubmed/?term=11064448
5. https://www.ncbi.nlm.nih.gov/pubmed/?term=15199672
6. https://www.ncbi.nlm.nih.gov/pubmed/?term=15476481
7. https://www.ncbi.nlm.nih.gov/pubmed/?term=15628319
8. https://www.ncbi.nlm.nih.gov/pubmed/?term=15973722
9. https://www.ncbi.nlm.nih.gov/pubmed/?term=16344342
10. https://www.ncbi.nlm.nih.gov/pubmed/?term=16397313
11. https://www.ncbi.nlm.nih.gov/pubmed/?term=16764353
12. https://www.ncbi.nlm.nih.gov/pubmed/?term=16954801
13. https://www.ncbi.nlm.nih.gov/pubmed/?term=17381669
14. https://www.ncbi.nlm.nih.gov/pubmed/?term=17970886
15. https://www.ncbi.nlm.nih.gov/pubmed/?term=18008354
16. https://www.ncbi.nlm.nih.gov/pubmed/?term=18336531
17. https://www.ncbi.nlm.nih.gov/pubmed/?term=19243907
18. https://www.ncbi.nlm.nih.gov/pubmed/?term=20080917
19. https://www.ncbi.nlm.nih.gov/pubmed/?term=25248004
20. https://www.ncbi.nlm.nih.gov/pubmed/?term=25314066
21. https://www.ncbi.nlm.nih.gov/pubmed/?term=25440430
22. https://www.ncbi.nlm.nih.gov/pubmed/?term=25443086
23. https://www.ncbi.nlm.nih.gov/pubmed/?term=25581826
24. https://www.ncbi.nlm.nih.gov/pubmed/?term=25641386
25. https://www.ncbi.nlm.nih.gov/pubmed/?term=28166217
26. https://www.ncbi.nlm.nih.gov/pubmed/?term=8738760
27. https://www.ncbi.nlm.nih.gov/pubmed/?term=9273463
28. https://www.ncbi.nlm.nih.gov/pubmed/?term=9345422