Identification

Name
Azathioprine
Accession Number
DB00993
Description

Azathioprine is a prodrug of 6-mercaptopurine, first synthesized in 1956 by Gertrude Elion, William Lange, and George Hitchings in an attempt to produce a derivative of 6-mercaptopurine with a better therapeutic index.9,10,11 Azathioprine is used to treat inflammatory conditions like rheumatoid arthritis and as an immunosuppressant in the prevention of renal transplant rejection.12

Azathiprine was granted FDA approval on 20 March 1968.12

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 277.263
Monoisotopic: 277.038193193
Chemical Formula
C9H7N7O2S
Synonyms
  • 6-((1-Methyl-4-nitro-1H-imidazol-5-yl)thio)-1H-purine
  • 6-(1'-Methyl-4'-nitro-5'-imidazolyl)-mercaptopurine
  • Azamun
  • Azathioprine
  • Azathioprinum
  • Azatioprina
External IDs
  • BW 57-322
  • BW-57-322
  • NSC-39084

Pharmacology

Indication

Azathioprine is indicated to treat rheumatoid arthritis and prevent renal transplant rejection.12

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Azathioprine is an immunosuppressive agent which functions through modulation of rac1 to induce T cell apoptosis, as well as other unknown immunosuppressive functions.5 It has a long duration of action as it is given daily, and has a narrow therapeutic index.12 Patients should be counselled regarding the risk of malignancies of the skin and lymphomas.12

Mechanism of action

Azathioprine's mechanism of action is not entirely understood but it may be related to inhibition of purine synthesis, along with inhibition of B and T cells.5

6-thioguanine triphosphate, a metabolite of azathioprine, modulates activation of rac1 when costimulated with CD28, inducing T cell apoptosis.5 This may be mediated through rac1's action on mitogen-activated protein kinase, NF-kappaB.5

TargetActionsOrganism
URas-related C3 botulinum toxin substrate 1
modulator
Humans
Absorption

Oral azathioprine is well absorbed, with a Tmax of 1-2h.12 Further data regarding the absorption of azathioprine is not readily available.6,7

Volume of distribution

Data regarding the volume of distribution of azathioprine is not readily available.6,7

Protein binding

Azathioprine is 30%12 bound to proteins such as human serum albumin in circulation.1

Metabolism

Azathioprine is converted to 6-mercaptopurine nonenzymatically.4 6-mercaptopurine is then metabolized to 6-methylmercaptopurine by thiopurine methyltransferase, 6-thiouric acid by xanthine oxidase, or 6-thiosine-5'-monophosphate by hypoxanthine phosphoribosyltransferase.4 6-thiosine-5'-monophosphate is metabolized to 6-methylthiosine-5'-monophosphate by thiopurine methyltransferase or 6-thioxanthylic acid by inosine monophosphate dehydrogenase.4 6-thioxanthylic acid is metabolized by guanosine monophosphate synthetase to 6-thioguanine monophosphate, the first of the 6-thioguanine nucleotides.4 6-thioguanine monophosphate is phosphorylated to produce the remaining 6-thioguanine nucleotides, 6-thioguanine diphosphate and 6-thioguanine triphosphate.4

Hover over products below to view reaction partners

Route of elimination

Azathioprine and mercaptopurine are not detectable in urine after 8 hours.12 Further data regarding the route of elimination of azathioprine are not available.8

Half-life

The half life of azathioprine is approximately 5 hours.12

Clearance

Data regarding the clearance of azathioprine is not readily available.6,7

Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
Toxicity

The oral LD50 in mice is 2500mg/kg and in rats is 400mg/kg.12

Patients experiencing an overdose may present with bone marrow hypoplasia, bleeding, and infection, which may progress to death.12 Patients should be treated with supportive and symptomatic treatments. 8 hour hemodialysis may remove 45% of a dose from serum.12

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Azathioprine Action PathwayDrug action
Azathioprine Metabolism PathwayDrug metabolism
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Thiopurine S-methyltransferaseTPMT*2(G;G) / (C;G)G AlleleADR Directly StudiedPatients with this genotype have reduced metabolism of azathioprine resulting in increased toxicity.Details
Thiopurine S-methyltransferaseTPMT*3A(A;A) / (A;G)A AlleleADR Directly StudiedPatients with this genotype have reduced metabolism of azathioprine resulting in increased toxicity.Details
Thiopurine S-methyltransferaseTPMT*3C(G;G) / (A;G)G AlleleADR Directly StudiedPatients with this genotype have reduced metabolism of azathioprine resulting in increased toxicity.Details
Thiopurine S-methyltransferaseTPMT*3BNot Availablec.460G>AADR InferredMyelosuppressionDetails
Thiopurine S-methyltransferaseTPMT*4ANot AvailableG > AADR InferredMyelosuppressionDetails

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirAzathioprine may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbametapirThe serum concentration of Azathioprine can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Azathioprine can be increased when combined with Abatacept.
AbirateroneThe serum concentration of Azathioprine can be increased when it is combined with Abiraterone.
AcarboseAcarbose may decrease the excretion rate of Azathioprine which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Azathioprine which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Azathioprine which could result in a higher serum level.
AcenocoumarolThe therapeutic efficacy of Acenocoumarol can be decreased when used in combination with Azathioprine.
AcetaminophenThe metabolism of Azathioprine can be decreased when combined with Acetaminophen.
AcetazolamideAcetazolamide may increase the excretion rate of Azathioprine which could result in a lower serum level and potentially a reduction in efficacy.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Take with food. Food reduces irritation.

Products

Product Ingredients
IngredientUNIICASInChI Key
Azathioprine sodiumAM94R510MS55774-33-9WISNYKIQFMKSDQ-UHFFFAOYSA-N
Product Images
International/Other Brands
Azamun (Ascent) / Azanin (Tanabe Mitsubishi Pharma) / Imurek (Aspen) / Imurel (GlaxoSmithKline)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AzathioprineTablet50 mgOralSanis Health Inc2010-02-162017-07-31Canada flag
AzathioprineTablet50 mgOralBdh Inc.1998-10-082000-08-03Canada flag
Azathioprine Sodium for InjectionPowder, for solutionIntravenousNovopharm LimitedNot applicableNot applicableCanada flag
Azathioprine-50TabletOralPro Doc Limitee2009-06-10Not applicableCanada flag
ImuranTablet50 mgOralAspen Pharmacare Canada Inc.1966-12-31Not applicableCanada flag
ImuranTablet50 mg/1OralPrometheus Laboratories1968-03-20Not applicableUS flag
ImuranPowder, for solution50 mgIntravenousAspen Pharmacare Canada Inc.2001-12-20Not applicableCanada flag
ImuranInjection, powder, lyophilized, for solution100 mg/1mLIntravenousPrometheus Laboratories1974-07-192001-05-21US flag
ImuranTablet50 mg/1OralSebela Pharmaceuticals Inc.2017-12-01Not applicableUS flag
ImuranTablet50 mg/1OralPhysicians Total Care, Inc.1968-03-202012-06-30US flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Apo-azathioprineTabletOralApotex Corporation2000-10-17Not applicableCanada flag
AzasanTablet100 mg/1OralSalix Pharmaceuticals Inc.2003-04-01Not applicableUS flag
AzasanTablet75 mg/1OralSalix Pharmaceuticals Inc.2003-04-01Not applicableUS flag
AzathioprineTablet50 1/1OralZydus Pharmaceuticals (USA) Inc.2007-07-11Not applicableUS flag68382 00320180913 8702 xv88r
AzathioprineTablet50 mg/1OralAmneal Pharmaceuticals NY LLC2015-02-022016-09-30US flag
AzathioprineTablet50 mg/1OralAphena Pharma Solutions - Tennessee, LLC1996-02-162017-04-01US flag
AzathioprineTablet50 mg/1OralAphena Pharma Solutions Tennessee, Inc.2009-12-28Not applicableUS flag
AzathioprineTablet50 mg/1OralAscend Laboratories, LLC2020-03-29Not applicableUS flag
AzathioprineTablet50 mg/1OralAidarex Pharmaceuticals LLC2007-07-11Not applicableUS flag
AzathioprineTablet50 mg/1OralCadila Healthcare Limited2007-07-11Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

ATC Codes
L04AX01 — Azathioprine
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
6-thiopurines / Nitroimidazoles / Nitroaromatic compounds / Pyrimidines and pyrimidine derivatives / Imidolactams / N-substituted imidazoles / Heteroaromatic compounds / Sulfenyl compounds / Propargyl-type 1,3-dipolar organic compounds / Azacyclic compounds
show 6 more
Substituents
6-thiopurine / Allyl-type 1,3-dipolar organic compound / Aromatic heteropolycyclic compound / Azacycle / Azole / C-nitro compound / Diarylthioether / Heteroaromatic compound / Hydrocarbon derivative / Imidazole
show 19 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
C-nitro compound, aryl sulfide, imidazoles, thiopurine (CHEBI:2948)

Chemical Identifiers

UNII
MRK240IY2L
CAS number
446-86-6
InChI Key
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)
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

References

General References
  1. Sochacka J: Docking of thiopurine derivatives to human serum albumin and binding site analysis with Molegro Virtual Docker. Acta Pol Pharm. 2014 Mar-Apr;71(2):343-9. [PubMed:25272656]
  2. Van Os EC, Zins BJ, Sandborn WJ, Mays DC, Tremaine WJ, Mahoney DW, Zinsmeister AR, Lipsky JJ: Azathioprine pharmacokinetics after intravenous, oral, delayed release oral and rectal foam administration. Gut. 1996 Jul;39(1):63-8. doi: 10.1136/gut.39.1.63. [PubMed:8881811]
  3. Anstey A, Lear JT: Azathioprine: clinical pharmacology and current indications in autoimmune disorders. BioDrugs. 1998 Jan;9(1):33-47. [PubMed:18020555]
  4. Dubinsky MC: Azathioprine, 6-mercaptopurine in inflammatory bowel disease: pharmacology, efficacy, and safety. Clin Gastroenterol Hepatol. 2004 Sep;2(9):731-43. [PubMed:15354273]
  5. Tiede I, Fritz G, Strand S, Poppe D, Dvorsky R, Strand D, Lehr HA, Wirtz S, Becker C, Atreya R, Mudter J, Hildner K, Bartsch B, Holtmann M, Blumberg R, Walczak H, Iven H, Galle PR, Ahmadian MR, Neurath MF: CD28-dependent Rac1 activation is the molecular target of azathioprine in primary human CD4+ T lymphocytes. J Clin Invest. 2003 Apr;111(8):1133-45. [PubMed:12697733]
  6. Stocco G, Martelossi S, Arrigo S, Barabino A, Aloi M, Martinelli M, Miele E, Knafelz D, Romano C, Naviglio S, Favretto D, Cuzzoni E, Franca R, Decorti G, Ventura A: Multicentric Case-Control Study on Azathioprine Dose and Pharmacokinetics in Early-onset Pediatric Inflammatory Bowel Disease. Inflamm Bowel Dis. 2017 Apr;23(4):628-634. doi: 10.1097/MIB.0000000000001051. [PubMed:28296824]
  7. Pelin M, Genova E, Fusco L, Marisat M, Hofmann U, Favretto D, Lucafo M, Taddio A, Martelossi S, Ventura A, Stocco G, Schwab M, Decorti G: Pharmacokinetics and pharmacodynamics of thiopurines in an in vitro model of human hepatocytes: Insights from an innovative mass spectrometry assay. Chem Biol Interact. 2017 Sep 25;275:189-195. doi: 10.1016/j.cbi.2017.08.009. Epub 2017 Aug 12. [PubMed:28811125]
  8. Schusziarra V, Ziekursch V, Schlamp R, Siemensen HC: Pharmacokinetics of azathioprine under haemodialysis. Int J Clin Pharmacol Biopharm. 1976 Dec;14(4):298-302. [PubMed:1002367]
  9. Wright S, Sanders DS, Lobo AJ, Lennard L: Clinical significance of azathioprine active metabolite concentrations in inflammatory bowel disease. Gut. 2004 Aug;53(8):1123-8. doi: 10.1136/gut.2003.032896. [PubMed:15247179]
  10. Elion GB: The purine path to chemotherapy. Science. 1989 Apr 7;244(4900):41-7. doi: 10.1126/science.2649979. [PubMed:2649979]
  11. Elion G, Lange W, Hitchings G: Studies on Condensed Pyrimidine Systems. XIII. Some Amino-substituted Derivatives of Guanine and 6-Thioguanine Journal of the American Chemical Society. 1956 Jan 1;78(1):217-220.
  12. FDA Approved Drug Products: Imuran Azathioprine Oral Tablets [Link]
Human Metabolome Database
HMDB0015128
KEGG Drug
D00238
KEGG Compound
C06837
PubChem Compound
2265
PubChem Substance
46508252
ChemSpider
2178
BindingDB
50373919
RxNav
1256
ChEBI
2948
ChEMBL
CHEMBL1542
ZINC
ZINC000004258316
Therapeutic Targets Database
DAP000782
PharmGKB
PA448515
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Azathioprine
AHFS Codes
  • 92:44.00 — Immunosuppressive Agents
FDA label
Download (212 KB)
MSDS
Download (75.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingHealth Services ResearchTransplantation, Liver1
4Active Not RecruitingTreatmentCrohn's Disease (CD)2
4Active Not RecruitingTreatmentHepatocellular Carcinoma1
4CompletedPreventionAcute Graft Rejection / Delayed Graft Function1
4CompletedPreventionDisorder Related to Cardiac Transplantation1
4CompletedTreatmentAllergic granulomatous angiitis / Churg-Strauss Syndrome / Granulomatosis With Polyangiitis / Microscopic Polyangiitis / Polyarteritis Nodosa / Vasculitis1
4CompletedTreatmentCrohn's Disease (CD)2
4CompletedTreatmentHepatitis, Autoimmune1
4CompletedTreatmentIgA Nephropathy1
4CompletedTreatmentImmune Thrombocytopenia1

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
  • AAIPharma Inc.
  • Amerisource Health Services Corp.
  • Bedford Labs
  • Ben Venue Laboratories Inc.
  • Cadila Healthcare Ltd.
  • Cardinal Health
  • Glenmark Generics Ltd.
  • Heartland Repack Services LLC
  • Mallinckrodt Inc.
  • Medisca Inc.
  • Mylan
  • Nucare Pharmaceuticals Inc.
  • Oso Biopharmaceuticals Manufacturing LLC
  • Pharmedix
  • Physicians Total Care Inc.
  • Prometheus Laboratories Inc.
  • Rebel Distributors Corp.
  • Resolution Chemicals Ltd.
  • Roxane Labs
  • Salix Pharmaceuticals
  • Sandoz
  • UDL Laboratories
  • Vangard Labs Inc.
  • Xanodyne Pharmaceuticals Inc.
  • Zydus Pharmaceuticals
Dosage Forms
FormRouteStrength
Tablet, film coatedOral50 MG
Tablet50 MG
Tablet, film coatedOral100 MG
Tablet, film coatedOral75 MG
TabletOral100 mg/1
TabletOral75 mg/1
Tablet, film coatedOral25 MG
PowderNot applicable1 g/1g
TabletOral100 1/1
TabletOral25 1/1
TabletOral25 mg/1
TabletOral50 1/1
TabletOral50 mg/1
TabletOral75 1/1
Tablet, film coatedOral50 mg/1
Injection, powder, lyophilized, for solutionIntravenous100 mg/10mL
Tablet, coatedOral50 mg
TabletOral50 mg
Injection, powder, lyophilized, for solutionIntravenous100 mg/1mL
Powder, for solutionIntravenous50 mg
Tablet25 mg
InjectionIntravenous50 mg
Tablet
Powder, for solutionIntravenous
TabletOral
Prices
Unit descriptionCostUnit
Azathioprine sod 100 mg vial132.0USD vial
Azathioprine powder28.15USD g
Azasan 100 mg tablet5.8USD tablet
Azasan 75 mg tablet4.34USD tablet
Imuran 50 mg Tablet2.76USD tablet
Azathioprine 50 mg tablet0.94USD tablet
Apo-Azathioprine 50 mg Tablet0.57USD tablet
Mylan-Azathioprine 50 mg Tablet0.57USD tablet
Novo-Azathioprine 50 mg Tablet0.57USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)243.5 °CPhysProp
water solubilityInsoluble FDA label
logP0.10HANSCH,C ET AL. (1995)
pKa7.87 (at 25 °C)MITRA,AK & NARURKAR,MM (1986)
Predicted Properties
PropertyValueSource
Water Solubility1.07 mg/mLALOGPS
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 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity70.95 m3·mol-1ChemAxon
Polarizability24.26 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9607
Blood Brain Barrier+0.9226
Caco-2 permeable+0.5057
P-glycoprotein substrateNon-substrate0.7766
P-glycoprotein inhibitor INon-inhibitor0.8049
P-glycoprotein inhibitor IINon-inhibitor0.6683
Renal organic cation transporterNon-inhibitor0.8493
CYP450 2C9 substrateNon-substrate0.7861
CYP450 2D6 substrateNon-substrate0.8273
CYP450 3A4 substrateNon-substrate0.5944
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.9733
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7
Ames testAMES toxic0.9152
CarcinogenicityNon-carcinogens0.9182
BiodegradationNot ready biodegradable0.9576
Rat acute toxicity2.7519 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7434
hERG inhibition (predictor II)Non-inhibitor0.8449
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-004i-0390000000-0d11d23373539cfb283c
MS/MS Spectrum - , positiveLC-MS/MSsplash10-000x-0950000000-b6de6073310270167ffb
MS/MS Spectrum - , positiveLC-MS/MSsplash10-001l-2950000000-4d3fb67844876c217814

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Modulator
General Function
Thioesterase binding
Specific Function
Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins to regulate cellular respon...
Gene Name
RAC1
Uniprot ID
P63000
Uniprot Name
Ras-related C3 botulinum toxin substrate 1
Molecular Weight
21449.895 Da
References
  1. Tiede I, Fritz G, Strand S, Poppe D, Dvorsky R, Strand D, Lehr HA, Wirtz S, Becker C, Atreya R, Mudter J, Hildner K, Bartsch B, Holtmann M, Blumberg R, Walczak H, Iven H, Galle PR, Ahmadian MR, Neurath MF: CD28-dependent Rac1 activation is the molecular target of azathioprine in primary human CD4+ T lymphocytes. J Clin Invest. 2003 Apr;111(8):1133-45. [PubMed:12697733]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
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...
Gene Name
HPRT1
Uniprot ID
P00492
Uniprot Name
Hypoxanthine-guanine phosphoribosyltransferase
Molecular Weight
24579.155 Da
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:15354273]
  2. Reuther LO, Sonne J, Larsen NE, Larsen B, Christensen S, Rasmussen SN, Tofteng F, Haaber A, Johansen N, Kjeldsen J, Schmiegelow K: Pharmacological monitoring of azathioprine therapy. Scand J Gastroenterol. 2003 Sep;38(9):972-7. doi: 10.1080/00365520310005082. [PubMed:14531535]
  3. FDA Approved Drug Products: Imuran Azathioprine Oral Tablets [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
May catalyze the hydrolysis of nucleoside triphosphates including dGTP, dTTP, dCTP, their oxidized forms like 8-oxo-dGTP and the prodrug thiopurine derivatives 6-thio-dGTP and 6-thio-GTP (PubMed:26238318). Could also catalyze the hydrolysis of some nucleoside diphosphate derivatives (PubMed:22556419, PubMed:26238318). Hydrolyzes oxidized nucleosides triphosphates like 8-oxo-dGTP in vitro, but the specificity and efficiency towards these substrates are low. Therefore, the potential in vivo sanitizing role of this enzyme, that would consist in removing oxidatively damaged forms of nucleosides to prevent their incorporation into DNA, is unclear (PubMed:26238318, PubMed:22556419). Through the hydrolysis of thioguanosine triphosphates may participate in the catabolism of thiopurine drugs (PubMed:26238318, PubMed:25108385). May also have a role in DNA synthesis and cell cycle progression by stabilizing PCNA (PubMed:19419956).
Specific Function
8-oxo-7,8-dihydrodeoxyguanosine triphosphate pyrophosphatase activity
Gene Name
NUDT15
Uniprot ID
Q9NV35
Uniprot Name
Nucleotide triphosphate diphosphatase NUDT15
Molecular Weight
18608.965 Da
References
  1. Reuther LO, Sonne J, Larsen NE, Larsen B, Christensen S, Rasmussen SN, Tofteng F, Haaber A, Johansen N, Kjeldsen J, Schmiegelow K: Pharmacological monitoring of azathioprine therapy. Scand J Gastroenterol. 2003 Sep;38(9):972-7. doi: 10.1080/00365520310005082. [PubMed:14531535]
  2. Stocco G, Pelin M, Franca R, De Iudicibus S, Cuzzoni E, Favretto D, Martelossi S, Ventura A, Decorti G: Pharmacogenetics of azathioprine in inflammatory bowel disease: a role for glutathione-S-transferase? World J Gastroenterol. 2014 Apr 7;20(13):3534-41. doi: 10.3748/wjg.v20.i13.3534. [PubMed:24707136]
  3. FDA Approved Drug Products: Imuran Azathioprine Oral Tablets [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Xanthine oxidase 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. Ha...
Gene Name
XDH
Uniprot ID
P47989
Uniprot Name
Xanthine dehydrogenase/oxidase
Molecular Weight
146422.99 Da
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:15354273]
  2. Reuther LO, Sonne J, Larsen NE, Larsen B, Christensen S, Rasmussen SN, Tofteng F, Haaber A, Johansen N, Kjeldsen J, Schmiegelow K: Pharmacological monitoring of azathioprine therapy. Scand J Gastroenterol. 2003 Sep;38(9):972-7. doi: 10.1080/00365520310005082. [PubMed:14531535]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Thiopurine s-methyltransferase activity
Specific Function
Catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine.
Gene Name
TPMT
Uniprot ID
P51580
Uniprot Name
Thiopurine S-methyltransferase
Molecular Weight
28180.09 Da
References
  1. 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]
  2. FDA Approved Drug Products: Imuran Azathioprine Oral Tablets [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Glutathione transferase activity
Specific Function
Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.
Gene Name
GSTA1
Uniprot ID
P08263
Uniprot Name
Glutathione S-transferase A1
Molecular Weight
25630.785 Da
References
  1. Stocco G, Pelin M, Franca R, De Iudicibus S, Cuzzoni E, Favretto D, Martelossi S, Ventura A, Decorti G: Pharmacogenetics of azathioprine in inflammatory bowel disease: a role for glutathione-S-transferase? World J Gastroenterol. 2014 Apr 7;20(13):3534-41. doi: 10.3748/wjg.v20.i13.3534. [PubMed:24707136]
  2. Lucafo M, Stocco G, Martelossi S, Favretto D, Franca R, Malusa N, Lora A, Bramuzzo M, Naviglio S, Cecchin E, Toffoli G, Ventura A, Decorti G: Azathioprine Biotransformation in Young Patients with Inflammatory Bowel Disease: Contribution of Glutathione-S Transferase M1 and A1 Variants. Genes (Basel). 2019 Apr 4;10(4). pii: genes10040277. doi: 10.3390/genes10040277. [PubMed:30987408]
  3. Link [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Glutathione transferase activity
Specific Function
Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.
Gene Name
GSTA2
Uniprot ID
P09210
Uniprot Name
Glutathione S-transferase A2
Molecular Weight
25663.675 Da
References
  1. Stocco G, Pelin M, Franca R, De Iudicibus S, Cuzzoni E, Favretto D, Martelossi S, Ventura A, Decorti G: Pharmacogenetics of azathioprine in inflammatory bowel disease: a role for glutathione-S-transferase? World J Gastroenterol. 2014 Apr 7;20(13):3534-41. doi: 10.3748/wjg.v20.i13.3534. [PubMed:24707136]
  2. Link [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Protein homodimerization activity
Specific Function
Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.
Gene Name
GSTM1
Uniprot ID
P09488
Uniprot Name
Glutathione S-transferase Mu 1
Molecular Weight
25711.555 Da
References
  1. Stocco G, Pelin M, Franca R, De Iudicibus S, Cuzzoni E, Favretto D, Martelossi S, Ventura A, Decorti G: Pharmacogenetics of azathioprine in inflammatory bowel disease: a role for glutathione-S-transferase? World J Gastroenterol. 2014 Apr 7;20(13):3534-41. doi: 10.3748/wjg.v20.i13.3534. [PubMed:24707136]
  2. Lucafo M, Stocco G, Martelossi S, Favretto D, Franca R, Malusa N, Lora A, Bramuzzo M, Naviglio S, Cecchin E, Toffoli G, Ventura A, Decorti G: Azathioprine Biotransformation in Young Patients with Inflammatory Bowel Disease: Contribution of Glutathione-S Transferase M1 and A1 Variants. Genes (Basel). 2019 Apr 4;10(4). pii: genes10040277. doi: 10.3390/genes10040277. [PubMed:30987408]
  3. Link [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Rna binding
Specific Function
Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore pl...
Gene Name
IMPDH1
Uniprot ID
P20839
Uniprot Name
Inosine-5'-monophosphate dehydrogenase 1
Molecular Weight
55405.365 Da
References
  1. Stocco G, Pelin M, Franca R, De Iudicibus S, Cuzzoni E, Favretto D, Martelossi S, Ventura A, Decorti G: Pharmacogenetics of azathioprine in inflammatory bowel disease: a role for glutathione-S-transferase? World J Gastroenterol. 2014 Apr 7;20(13):3534-41. doi: 10.3748/wjg.v20.i13.3534. [PubMed:24707136]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Rna binding
Specific Function
Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore pl...
Gene Name
IMPDH2
Uniprot ID
P12268
Uniprot Name
Inosine-5'-monophosphate dehydrogenase 2
Molecular Weight
55804.495 Da
References
  1. Stocco G, Pelin M, Franca R, De Iudicibus S, Cuzzoni E, Favretto D, Martelossi S, Ventura A, Decorti G: Pharmacogenetics of azathioprine in inflammatory bowel disease: a role for glutathione-S-transferase? World J Gastroenterol. 2014 Apr 7;20(13):3534-41. doi: 10.3748/wjg.v20.i13.3534. [PubMed:24707136]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Pyrophosphatase activity
Specific Function
Involved in the de novo synthesis of guanine nucleotides which are not only essential for DNA and RNA synthesis, but also provide GTP, which is involved in a number of cellular processes important ...
Gene Name
GMPS
Uniprot ID
P49915
Uniprot Name
GMP synthase [glutamine-hydrolyzing]
Molecular Weight
76714.79 Da
References
  1. Stocco G, Pelin M, Franca R, De Iudicibus S, Cuzzoni E, Favretto D, Martelossi S, Ventura A, Decorti G: Pharmacogenetics of azathioprine in inflammatory bowel disease: a role for glutathione-S-transferase? World J Gastroenterol. 2014 Apr 7;20(13):3534-41. doi: 10.3748/wjg.v20.i13.3534. [PubMed:24707136]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Xtp diphosphatase activity
Specific Function
Pyrophosphatase that hydrolyzes the non-canonical purine nucleotides inosine triphosphate (ITP), deoxyinosine triphosphate (dITP) as well as 2'-deoxy-N-6-hydroxylaminopurine triposphate (dHAPTP) an...
Gene Name
ITPA
Uniprot ID
Q9BY32
Uniprot Name
Inosine triphosphate pyrophosphatase
Molecular Weight
21445.495 Da
References
  1. Stocco G, Pelin M, Franca R, De Iudicibus S, Cuzzoni E, Favretto D, Martelossi S, Ventura A, Decorti G: Pharmacogenetics of azathioprine in inflammatory bowel disease: a role for glutathione-S-transferase? World J Gastroenterol. 2014 Apr 7;20(13):3534-41. doi: 10.3748/wjg.v20.i13.3534. [PubMed:24707136]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Lampe JW, King IB, Li S, Grate MT, Barale KV, Chen C, Feng Z, Potter JD: Brassica vegetables increase and apiaceous vegetables decrease cytochrome P450 1A2 activity in humans: changes in caffeine metabolite ratios in response to controlled vegetable diets. Carcinogenesis. 2000 Jun;21(6):1157-62. [PubMed:10837004]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Sochacka J: Docking of thiopurine derivatives to human serum albumin and binding site analysis with Molegro Virtual Docker. Acta Pol Pharm. 2014 Mar-Apr;71(2):343-9. [PubMed:25272656]
  2. Tanaka M, Asahi Y, Masuda S, Ota T: Binding position of azathioprine with bovine serum albumin determined by measuring nuclear magnetic resonance relaxation time. Chem Pharm Bull (Tokyo). 1991 Nov;39(11):2771-4. doi: 10.1248/cpb.39.2771. [PubMed:1799934]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Nucleoside transmembrane transporter activity
Specific Function
Mediates equilibrative transport of purine, pyrimidine nucleosides and the purine base hypoxanthine. Very less sensitive than SLC29A1 to inhibition by nitrobenzylthioinosine (NBMPR), dipyridamole, ...
Gene Name
SLC29A2
Uniprot ID
Q14542
Uniprot Name
Equilibrative nucleoside transporter 2
Molecular Weight
50112.335 Da
References
  1. Conklin LS, Cuffari C, Okazaki T, Miao Y, Saatian B, Chen TE, Tse M, Brant SR, Li X: 6-Mercaptopurine transport in human lymphocytes: correlation with drug-induced cytotoxicity. J Dig Dis. 2012 Feb;13(2):82-93. doi: 10.1111/j.1751-2980.2011.00556.x. [PubMed:22257476]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Pyrimidine- and adenine-specific:sodium symporter activity
Specific Function
Sodium-dependent, pyrimidine- and purine-selective. Involved in the homeostasis of endogenous nucleosides. Exhibits the transport characteristics of the nucleoside transport system cib or N3 subtyp...
Gene Name
SLC28A3
Uniprot ID
Q9HAS3
Uniprot Name
Solute carrier family 28 member 3
Molecular Weight
76929.61 Da
References
  1. Conklin LS, Cuffari C, Okazaki T, Miao Y, Saatian B, Chen TE, Tse M, Brant SR, Li X: 6-Mercaptopurine transport in human lymphocytes: correlation with drug-induced cytotoxicity. J Dig Dis. 2012 Feb;13(2):82-93. doi: 10.1111/j.1751-2980.2011.00556.x. [PubMed:22257476]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Conklin LS, Cuffari C, Okazaki T, Miao Y, Saatian B, Chen TE, Tse M, Brant SR, Li X: 6-Mercaptopurine transport in human lymphocytes: correlation with drug-induced cytotoxicity. J Dig Dis. 2012 Feb;13(2):82-93. doi: 10.1111/j.1751-2980.2011.00556.x. [PubMed:22257476]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Putative transporter.
Specific Function
Not Available
Gene Name
SLC43A3
Uniprot ID
Q8NBI5
Uniprot Name
Solute carrier family 43 member 3
Molecular Weight
54528.23 Da
References
  1. Ruel NM, Nguyen KH, Vilas G, Hammond JR: Characterization of 6-Mercaptopurine Transport by the SLC43A3-Encoded Nucleobase Transporter. Mol Pharmacol. 2019 Jun;95(6):584-596. doi: 10.1124/mol.118.114389. Epub 2019 Mar 25. [PubMed:30910793]

Drug created on June 13, 2005 07:24 / Updated on September 22, 2020 02:11

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