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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
Salts Not Available
Brand names
Name Company
Azamun
Azanin
Azasan
Ccucol
Imuran
Imurek
Imurel
Muran
Brand 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.
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
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 243.5 °C PhysProp
water solubility 272 mg/L Not Available
logP 0.10 HANSCH,C ET AL. (1995)
pKa 7.87 (at 25 °C) MITRA,AK & NARURKAR,MM (1986)
Predicted Properties
Property Value Source
water solubility 1.07e+00 g/l ALOGPS
logP 0.84 ALOGPS
logP 1.17 ChemAxon
logS -2.4 ALOGPS
pKa (strongest acidic) 8.65 ChemAxon
pKa (strongest basic) 4 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 6 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 118.1 ChemAxon
rotatable bond count 3 ChemAxon
refractivity 70.95 ChemAxon
polarizability 24.26 ChemAxon
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 KB)
MSDS show (75.4 KB)
Interactions
Drug Interactions
Drug Interaction
Acenocoumarol Azathioprine may decrease the anticoagulant effect of acenocoumarol.
Allopurinol Allopurinol may increase the effect of thiopurine, azathioprine.
Aminosalicylic Acid Aminosalicylic acid may increase the toxicity of thiopurine, azathioprine.
Anisindione Azathioprine may decrease the anticoagulant effect of anisindione.
Atracurium The agent decreases the effect of the muscle relaxant
Dicumarol Azathioprine may decrease the anticoagulant effect of dicumarol.
Doxacurium chloride The agent decreases the effect of the muscle relaxant
Febuxostat Coadministration of febuxostat with xanthine oxidase substrate drugs (azathioprine, mercaptopurine or theophylline) could increase plasma concentrations of these drugs, since these drugs are metabolized by xanthine oxidase, resulting in severe toxicity; hence their concomitant use is contraindicated. Since febuxostat does not inhibit or induce cytochrome P450 enzymes it lacks significant drug interactions with other drugs metabolized of these enzymes.
Mesalazine Mesalazine may increase the toxicity of thiopurine, azathioprine.
Metocurine The agent decreases the effect of the muscle relaxant
Mivacurium The agent decreases the effect of the muscle relaxant
Olsalazine Olsalazine may increase the toxicity of thiopurine, azathioprine.
Pancuronium The agent decreases the effect of the muscle relaxant
Rilonacept results in increased immunosuppressive effects; increases the risk of infection.
Sulfasalazine Sulfasalazine may increase the toxicity of thiopurine, azathioprine.
Trandolapril Trandolapril may increase the risk of neutropenia. Monitor for increased toxic effects of Azathioprine if Trandolapril is initiated or dose increased.
Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Tubocurarine The agent decreases the effect of the muscle relaxant
Vecuronium The agent decreases the effect of the muscle relaxant
Warfarin Azathioprine may decrease the anticoagulant effect of warfarin.
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 February 08, 2013 16:19