Human Metabolome Database: Showing metabocard for Azathioprine (HMDB0015128)

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Identification Taxonomy Ontology Physical properties Spectra Biological properties Concentrations Links References enzymes (3) Show 3 proteins XML

enzymes (3) Show 3 proteins

Record Information

Version

4.0

Creation Date

2012-09-06 15:16:51 UTC

Update Date

2017-10-23 19:06:27 UTC

HMDB ID

HMDB0015128

Secondary Accession Numbers

HMDB15128

Metabolite Identification

Common Name

Azathioprine

Description

Azathioprine 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.

Structure

MOL SDF 3D-SDF PDB SMILES InChI View 3D Structure

Synonyms

Value	Source
6-((1-Methyl-4-nitro-1H-imidazol-5-yl)thio)-1H-purine	ChEBI
6-(1'-Methyl-4'-nitro-5'-imidazolyl)-mercaptopurine	ChEBI
Imuran	ChEBI
Azathioprin	HMDB
Azatioprin	HMDB
Azothioprine	HMDB
Azathioprine sodium salt	MeSH
Azathioprine sodium	MeSH
Azathioprine sulfate	MeSH
Immuran	MeSH
Imurel	MeSH
Sodium, azathioprine	MeSH

Chemical Formula

C₉H₇N₇O₂S

Average Molecular Weight

277.263

Monoisotopic Molecular Weight

277.038193193

IUPAC Name

6-[(1-methyl-4-nitro-1H-imidazol-5-yl)sulfanyl]-7H-purine

Traditional Name

azathioprine

CAS Registry Number

446-86-6

SMILES

CN1C=NC(=C1SC1=NC=NC2=C1NC=N2)[N+]([O-])=O

InChI Identifier

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)

InChI Key

LMEKQMALGUDUQG-UHFFFAOYSA-N

Chemical Taxonomy

Description

This compound 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.

Kingdom

Organic compounds

Super Class

Organosulfur compounds

Class

Thioethers

Sub Class

Aryl thioethers

Direct Parent

Diarylthioethers

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 Framework

Aromatic heteropolycyclic compounds

External Descriptors

C-nitro compound (CHEBI:2948 )
aryl sulfide (CHEBI:2948 )
imidazoles (CHEBI:2948 )
thiopurine (CHEBI:2948 )

Ontology

Disposition

Biological Location:

Subcellular:

Cytoplasm

Biofluid and excreta:

Route of exposure:

Enteral:

Ingestion

Process

Naturally occurring process:

Biological process:

Biochemical pathway:

Role

Industrial application:

Drug

Pharmaceutical industry:

Pharmaceutical

Indirect biological role:

Poison

Physical Properties

State

Solid

Experimental Properties

Property	Value	Reference
Melting Point	243.5 °C	Not Available
Boiling Point	Not Available	Not Available
Water Solubility	1.07 g/L	Not Available
LogP	0.7	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	1.07 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 Å²	ChemAxon
Rotatable Bond Count	3	ChemAxon
Refractivity	70.95 m³·mol⁻¹	ChemAxon
Polarizability	24.26 Å³	ChemAxon
Number of Rings	3	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-004i-9680000000-14a922ede69208f7d93d	View in MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-qTof , Positive	splash10-001l-2950000000-4d3fb67844876c217814	View in MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-qTof , Positive	splash10-000x-0950000000-b6de6073310270167ffb	View in MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , negative	splash10-004i-0390000000-0d11d23373539cfb283c	View in MoNA
LC-MS/MS	LC-MS/MS Spectrum - , positive	splash10-000x-0950000000-b6de6073310270167ffb	View in MoNA
LC-MS/MS	LC-MS/MS Spectrum - , positive	splash10-001l-2950000000-4d3fb67844876c217814	View in MoNA
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-004i-0090000000-127672e50f7d85ca7302	View in MoNA
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-05i0-0090000000-7bb3b92e927e16854e1d	View in MoNA
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0a4i-9120000000-e50a6491ae4f28b8eeb0	View in MoNA
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-004i-3090000000-df6cb72af7b792b5cdfb	View in MoNA
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-004i-2490000000-b8ce493eef32ac50f458	View in MoNA
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-00ba-5910000000-2134d4c288ab79f6a689	View in MoNA

Biological Properties

Cellular Locations

Cytoplasm

Biofluid Locations

Blood
Urine

Tissue Location

Not Available

Pathways

Name	SMPDB/Pathwhiz	KEGG
Azathioprine Metabolism Pathway		Not Available
Azathioprine Pathway		Not Available

Displaying all 2 entries

Normal Concentrations

Biofluid	Status	Value	Age	Sex	Condition	Reference	Details
Blood	Expected but not Quantified		Not Available	Not Available	Taking drug identified by DrugBank entry DB00993	21059682	details
Urine	Expected but not Quantified		Not Available	Not Available	Taking drug identified by DrugBank entry DB00993	21059682	details

Abnormal Concentrations

Not Available

Predicted Concentrations

Biofluid	Value	Original age	Original sex	Original condition	Comments
Blood	0-4 uM	Adult (>18 years old)	Both	Normal	Predicted based on drug qualities
Blood	0-2 umol/mmol creatinine	Adult (>18 years old)	Both	Normal	Predicted based on drug qualities

Associated Disorders and Diseases

Disease References

None

Associated OMIM IDs

None

External Links

DrugBank ID

DB00993

DrugBank Metabolite ID

Not Available

Phenol Explorer Compound ID

Not Available

Phenol Explorer Metabolite ID

Not Available

FoodDB ID

Not Available

KNApSAcK ID

Not Available

Chemspider ID

2178

KEGG Compound ID

C06837

BioCyc ID

Not Available

BiGG ID

Not Available

Wikipedia Link

Azathioprine

METLIN ID

Not Available

PubChem Compound

2265

PDB ID

Not Available

ChEBI ID

2948

References

Synthesis Reference

Not Available

Material Safety Data Sheet (MSDS)

Download (PDF)

General References

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:15899149 ]
Gombar VK, Enslein K, Blake BW: Carcinogenicity of azathioprine: an S-AR investigation. Mutat Res. 1993 May;302(1):7-12. [PubMed:7683109 ]
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:15705694 ]

Enzymes

Enzyme Details

1. Xanthine dehydrogenase/oxidase

General function:: Involved in oxidoreductase activity
Specific function:: Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species. Has also low oxidase activity towards aldehydes (in vitro).
Gene Name:: XDH
Uniprot ID:: P47989
Molecular weight:: 146422.99

References

Dubinsky MC: Azathioprine, 6-mercaptopurine in inflammatory bowel disease: pharmacology, efficacy, and safety. Clin Gastroenterol Hepatol. 2004 Sep;2(9):731-43. [PubMed:15354273 ]

Enzyme Details

2. Thiopurine S-methyltransferase

General function:: Involved in thiopurine S-methyltransferase activity
Specific function:: Catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine.
Gene Name:: TPMT
Uniprot ID:: P51580
Molecular weight:: 28180.09

References

Sahasranaman S, Howard D, Roy S: Clinical pharmacology and pharmacogenetics of thiopurines. Eur J Clin Pharmacol. 2008 Aug;64(8):753-67. doi: 10.1007/s00228-008-0478-6. Epub 2008 May 28. [PubMed:18506437 ]

Enzyme Details

3. Hypoxanthine-guanine phosphoribosyltransferase

General function:: Involved in hypoxanthine phosphoribosyltransferase 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

References

Anstey A, Lear JT: Azathioprine: clinical pharmacology and current indications in autoimmune disorders. BioDrugs. 1998 Jan;9(1):33-47. [PubMed:18020555 ]
Dubinsky MC: Azathioprine, 6-mercaptopurine in inflammatory bowel disease: pharmacology, efficacy, and safety. Clin Gastroenterol Hepatol. 2004 Sep;2(9):731-43. [PubMed:15354273 ]

Showing metabocard for Azathioprine (HMDB0015128)

Structure for HMDB0015128 (Azathioprine)

Enzymes

References

References

References