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Identification
Name Azathioprine
Accession Number DB00993 (APRD00811)
Type small molecule
Groups approved
Description

An immunosuppressive pro-drug. It is converted into 6-mercaptopurine in the body where it blocks purine metabolism and DNA synthesis.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Azathioprin
  • Azathioprine Sodium
  • Azatioprin
  • Azothioprine
Brand names
  • Azamun
  • Azanin
  • Azasan
  • Ccucol
  • Imuran
  • Imurek
  • Imurel
  • Muran
Brand name mixtures Not Available
Categories
  • Antirheumatic Agents
  • Antimetabolites
  • Immunosuppressive Agents
  • Antimetabolites, Antineoplastic
CAS number 446-86-6
Weight Average: 277.263
Monoisotopic: 277.038193193
Chemical Formula C9H7N7O2S
InChI Key InChIKey=LMEKQMALGUDUQG-UHFFFAOYSA-N
InChI
InChI=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)
Plain Text
IUPAC Name
6-[(1-methyl-4-nitro-1H-imidazol-5-yl)sulfanyl]-7H-purine
SMILES
CN1C=NC(=C1SC1=NC=NC2=C1NC=N2)[N+]([O-])=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Nitroimidazoles
  • Purines and Purine Derivatives
Substructures
  • Nitroimidazoles
  • Ethers
  • Oxoazaniums
  • Nitro compounds
  • Pyrimidines and Derivatives
  • Imidazoles
  • Heterocyclic compounds
  • Aromatic compounds
  • Purines and Purine Derivatives
  • Cyanamides
Pharmacology
Indication For use in rheumatoid arthritis, preventing renal transplant rejection, Crohn's disease, and colitis.
Pharmacodynamics Azathioprine is a chemotherapy drug, now rarely used for chemotherapy but more for immunosuppression in organ transplantation and autoimmune disease such as rheumatoid arthritis or inflammatory bowel disease or Crohn's disease. It is a pro-drug, converted in the body to the active metabolite 6-mercaptopurine. Azathioprine acts to inhibit purine synthesis necessary for the proliferation of cells, especially leukocytes and lymphocytes. It is a safe and effective drug used alone in certain autoimmune diseases, or in combination with other immunosuppressants in organ transplantation. Its most severe side effect is bone marrow suppression, and it should not be given in conjunction with purine analogues such as allopurinol. The enzyme thiopurine S-methyltransferase (TPMT) deactivates 6-mercaptopurine. Genetic polymorphisms of TPMT can lead to excessive drug toxicity, thus assay of serum TPMT may be useful to prevent this complication.
Mechanism of action 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.
Absorption Well absorbed following oral administration.
Volume of distribution Not Available
Protein binding Azathioprine and the metabolite mercaptopurine are moderately bound to serum proteins (30%).
Metabolism

Primarily converted to the active metabolites 6-mercaptopurine and 6-thioinosinic acid via a non-enzymatica process. 6-mercaptopurine is subsequently metabolized primarily by xanthine oxidase.

Enzyme Metabolite Reaction Km Vmax
Thiopurine S-methyltransferase S-methylazathioprine S-methylation
Route of elimination Not Available
Half life Approximately 5 hours for the unchanged drug and its metabolites.
Clearance Not Available
Toxicity The oral LD50 for single doses of azathioprine in mice and rats are 2500 mg/kg and 400 mg/kg, respectively. Very large doses of this antimetabolite may lead to marrow hypoplasia, bleeding, infection, and death.
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00427 Azathioprine Pathway SMP00427
Pharmacoeconomics
Manufacturers
  • Aaipharma llc
  • Mylan pharmaceuticals inc
  • Roxane laboratories inc
  • Zydus pharmaceuticals usa inc
  • Prometheus laboratories inc
  • Bedford laboratories div ben venue laboratories inc
Packagers
Dosage forms
Form Route Strength
Powder, for solution Intravenous
Tablet Oral
Prices
Unit description Cost Unit
Azathioprine sod 100 mg vial 132.0 USD vial
Azathioprine powder 28.15 USD g
Azasan 100 mg tablet 5.8 USD tablet
Azasan 75 mg tablet 4.34 USD tablet
Imuran 50 mg Tablet 2.76 USD tablet
Azathioprine 50 mg tablet 0.94 USD tablet
Apo-Azathioprine 50 mg Tablet 0.57 USD tablet
Mylan-Azathioprine 50 mg Tablet 0.57 USD tablet
Novo-Azathioprine 50 mg Tablet 0.57 USD tablet
Patents Not Available
Properties
State solid
Melting point 243.5 oC
Experimental Properties
Property Value Source
water solubility 272 mg/L PhysProp
logP 0.7 PhysProp
Predicted Properties
Property Value Source
water solubility 1.07e+00 g/l ALOGPS
logP 0.84 ALOGPS
logP 1.17 ChemAxon Molconvert
logS -2.41 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 6 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 118.10 ChemAxon Molconvert
rotatable bond count 3 ChemAxon Molconvert
refractivity 70.95 ChemAxon Molconvert
polarizability 24.26 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  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. Pubmed
  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. Pubmed
  3. Gombar VK, Enslein K, Blake BW: Carcinogenicity of azathioprine: an S-AR investigation. Mutat Res. 1993 May;302(1):7-12. Pubmed
External Links
Resource Link
KEGG Drug D00238 Link_out
PubChem Compound 2265 Link_out
PubChem Substance 46508252 Link_out
ChemSpider 2178 Link_out
ChEBI 2948 Link_out
ChEMBL 2948 Link_out
Therapeutic Targets Database DAP000782 Link_out
PharmGKB PA448515 Link_out
Drug Product Database 2242907 Link_out
RxList http://www.rxlist.com/cgi/generic/azathioprine.htm Link_out
Drugs.com http://www.drugs.com/cdi/azathioprine.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Azathioprine Link_out
ATC Codes
  • L04AX01
AHFS Codes
  • 92:00.00
PDB Entries Not Available
FDA label show (212.1 KB)
MSDS show (75.4 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Take with food to reduce irritation.
Targets

1. Hypoxanthine-guanine phosphoribosyltransferase

Pharmacological action: yes
Actions: inhibitor
Organism class: human
UniProt ID: P00492 Link_out
Gene: HPRT1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Anstey A, Lear JT: Azathioprine: clinical pharmacology and current indications in autoimmune disorders. BioDrugs. 1998 Jan;9(1):33-47. Pubmed
  2. Dubinsky MC: Azathioprine, 6-mercaptopurine in inflammatory bowel disease: pharmacology, efficacy, and safety. Clin Gastroenterol Hepatol. 2004 Sep;2(9):731-43. Pubmed
Enzymes

1. Xanthine dehydrogenase/oxidase

Actions: substrate

This enzyme can be converted from the dehydrogenase form (D) to the oxidase form (O) irreversibly by proteolysis or reversibly through the oxidation of sulfhydryl groups

UniProt ID: P47989 Link_out
Gene: XDH Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Dubinsky MC: Azathioprine, 6-mercaptopurine in inflammatory bowel disease: pharmacology, efficacy, and safety. Clin Gastroenterol Hepatol. 2004 Sep;2(9):731-43. Pubmed

2. Thiopurine S-methyltransferase

Actions: substrate

Catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine

UniProt ID: P51580 Link_out
Gene: TPMT Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Sahasranaman S, Howard D, Roy S: Clinical pharmacology and pharmacogenetics of thiopurines. Eur J Clin Pharmacol. 2008 Aug;64(8):753-67. Epub 2008 May 28. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:07

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.