Azathioprine

Details

Stereochemistry	ACHIRAL
Molecular Formula	C9H7N7O2S
Molecular Weight	277.263
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1C=NC(=C1SC2=C3N=CNC3=NC=N2)[N+]([O-])=O

InChI

InChIKey=LMEKQMALGUDUQG-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Molecular Formula	C9H7N7O2S
Molecular Weight	277.263
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/016324s037,017391s016lbl.pdf
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/18020555

Azathioprine remains one of the most important and widely prescribed drugs for immunosuppression/immunomodulation in autoimmune disease over 30 years after its introduction. Azathioprine is licensed for the treatment of only a limited range of autoimmune disorders, which is probably a reflection on the age of the drug. Widening the license for a drug is both costly and time consuming, and it would make no commercial sense for manufacturers to do so, at this late stage of life, for azathioprine. However, azathioprine is now so well established as an immunomodulating drug in autoimmune disorders that it represents the gold standard by which other drugs are compared. Azathioprine is indicated as an adjunct for the prevention of rejection in renal homotransplantation. It is also indicated for the management of active rheumatoid arthritis to reduce signs and symptoms. The combined use of azathioprine tablets with disease modifying anti-rheumatic drugs (DMARDs) has not been studied for either added benefit or unexpected adverse effects. The use of azathioprine tablets with these agents cannot be recommended. Azathioprine 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. Azathioprine is metabolized to 6-mercaptopurine (6-MP). 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. 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.

CNS Activity

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Hypoxanthine-guanine phosphoribosyltransferase 4 Target ID: CHEMBL2360 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/016324s037,017391s016lbl.pdf	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Rheumatoid arthritis 320 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/016324s037,017391s016lbl.pdf	Palliative		Approved 8583	IMURAN Approved Use Azathioprine tablets are indicated as an adjunct for the prevention of rejection in renal homotransplantation. It is also indicated for the management of active rheumatoid arthritis to reduce signs and symptoms. Renal Homotransplantation Azathioprine tablets are indicated as an adjunct for the prevention of rejection in renal homotransplantation. Experience with over 16,000 transplants shows a 5-year patient survival of 35% to 55%, but this is dependent on donor, match for HLA antigens, anti-donor or anti-B-cell alloantigen antibody, and other variables. The effect of azathioprine tablets on these variables has not been tested in controlled trials. Rheumatoid Arthritis Azathioprine tablets are indicated for the treatment of active rheumatoid arthritis (RA) to reduce signs and symptoms. Aspirin, non-steroidal anti-inflammatory drugs and/or low dose glucocorticoids may be continued during treatment with azathioprine tablets. The combined use of azathioprine tablets with disease modifying anti-rheumatic drugs (DMARDs) has not been studied for either added benefit or unexpected adverse effects. The use of azathioprine tablets with these agents cannot be recommended. Launch Date 1968

C_max

Value	Dose	Co-administered	Analyte	Population
16.9 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8881811/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		MERCAPTOPURINE ANHYDROUS plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
64.8 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/9048271	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		MERCAPTOPURINE ANHYDROUS plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
41.6 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8881811/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	MERCAPTOPURINE ANHYDROUS plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
116 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8881811/	50 mg single, intravenous dose: 50 mg route of administration: Intravenous experiment type: SINGLE co-administered:	MERCAPTOPURINE ANHYDROUS plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
137.7 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/9048271	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	MERCAPTOPURINE ANHYDROUS plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8881811/	50 mg single, intravenous dose: 50 mg route of administration: Intravenous experiment type: SINGLE co-administered:		MERCAPTOPURINE ANHYDROUS plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
5 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/016324s039lbl.pdf	single, oral		AZATHIOPRINE serum	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
70% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/016324s039lbl.pdf	single, oral		AZATHIOPRINE serum	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
2 mg/kg 1 times / day multiple, oral Recommended Dose: 2 mg/kg, 1 times / day Route: oral Route: multiple Dose: 2 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15362028	unhealthy, 18–70 Health Status: unhealthy Age Group: 18–70 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/15362028	Disc. AE: Discomfort epigastric, Serum transaminase increased... AEs leading to discontinuation/dose reduction: Discomfort epigastric (severe, 1.4%) Serum transaminase increased (5.6%) Leukopenia (9.9%) Pancreatitis (acute, 4.2%) Thrombocytopenia (1.4%) Sources: https://pubmed.ncbi.nlm.nih.gov/15362028
2 mg/kg 1 times / day multiple, oral Recommended Dose: 2 mg/kg, 1 times / day Route: oral Route: multiple Dose: 2 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19109574	unhealthy, 25.2–78.6 Health Status: unhealthy Age Group: 25.2–78.6 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/19109574	Disc. AE: Hepatotoxicity, Digestion impaired... AEs leading to discontinuation/dose reduction: Hepatotoxicity (6.3%) Digestion impaired (4.8%) Sources: https://pubmed.ncbi.nlm.nih.gov/19109574
7500 mg single, oral Overdose Dose: 7500 mg Route: oral Route: single Dose: 7500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/4588639	unhealthy, 44 Health Status: unhealthy Age Group: 44 Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/4588639	Disc. AE: Vomiting, Diarrhea... AEs leading to discontinuation/dose reduction: Vomiting (mild) Diarrhea (mild) Sources: https://pubmed.ncbi.nlm.nih.gov/4588639
5 mg/kg 1 times / day multiple, oral Recommended Dose: 5 mg/kg, 1 times / day Route: oral Route: multiple Dose: 5 mg/kg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/016324s039lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/016324s039lbl.pdf	Disc. AE: Malignant neoplasm NOS, Lymphoma... AEs leading to discontinuation/dose reduction: Malignant neoplasm NOS Lymphoma Hepatosplenic T-cell lymphoma Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/016324s039lbl.pdf

AEs

AE	Significance	Dose	Population
Thrombocytopenia	1.4% Disc. AE	2 mg/kg 1 times / day multiple, oral Recommended Dose: 2 mg/kg, 1 times / day Route: oral Route: multiple Dose: 2 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15362028	unhealthy, 18–70 Health Status: unhealthy Age Group: 18–70 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/15362028
Serum transaminase increased	5.6% Disc. AE	2 mg/kg 1 times / day multiple, oral Recommended Dose: 2 mg/kg, 1 times / day Route: oral Route: multiple Dose: 2 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15362028	unhealthy, 18–70 Health Status: unhealthy Age Group: 18–70 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/15362028
Leukopenia	9.9% Disc. AE	2 mg/kg 1 times / day multiple, oral Recommended Dose: 2 mg/kg, 1 times / day Route: oral Route: multiple Dose: 2 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15362028	unhealthy, 18–70 Health Status: unhealthy Age Group: 18–70 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/15362028
Pancreatitis	acute, 4.2% Disc. AE	2 mg/kg 1 times / day multiple, oral Recommended Dose: 2 mg/kg, 1 times / day Route: oral Route: multiple Dose: 2 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15362028	unhealthy, 18–70 Health Status: unhealthy Age Group: 18–70 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/15362028
Discomfort epigastric	severe, 1.4% Disc. AE	2 mg/kg 1 times / day multiple, oral Recommended Dose: 2 mg/kg, 1 times / day Route: oral Route: multiple Dose: 2 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15362028	unhealthy, 18–70 Health Status: unhealthy Age Group: 18–70 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/15362028
Digestion impaired	4.8% Disc. AE	2 mg/kg 1 times / day multiple, oral Recommended Dose: 2 mg/kg, 1 times / day Route: oral Route: multiple Dose: 2 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19109574	unhealthy, 25.2–78.6 Health Status: unhealthy Age Group: 25.2–78.6 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/19109574
Hepatotoxicity	6.3% Disc. AE	2 mg/kg 1 times / day multiple, oral Recommended Dose: 2 mg/kg, 1 times / day Route: oral Route: multiple Dose: 2 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19109574	unhealthy, 25.2–78.6 Health Status: unhealthy Age Group: 25.2–78.6 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/19109574
Diarrhea	mild Disc. AE	7500 mg single, oral Overdose Dose: 7500 mg Route: oral Route: single Dose: 7500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/4588639	unhealthy, 44 Health Status: unhealthy Age Group: 44 Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/4588639
Vomiting	mild Disc. AE	7500 mg single, oral Overdose Dose: 7500 mg Route: oral Route: single Dose: 7500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/4588639	unhealthy, 44 Health Status: unhealthy Age Group: 44 Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/4588639
Hepatosplenic T-cell lymphoma	Disc. AE	5 mg/kg 1 times / day multiple, oral Recommended Dose: 5 mg/kg, 1 times / day Route: oral Route: multiple Dose: 5 mg/kg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/016324s039lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/016324s039lbl.pdf
Lymphoma	Disc. AE	5 mg/kg 1 times / day multiple, oral Recommended Dose: 5 mg/kg, 1 times / day Route: oral Route: multiple Dose: 5 mg/kg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/016324s039lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/016324s039lbl.pdf
Malignant neoplasm NOS	Disc. AE	5 mg/kg 1 times / day multiple, oral Recommended Dose: 5 mg/kg, 1 times / day Route: oral Route: multiple Dose: 5 mg/kg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/016324s039lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/016324s039lbl.pdf

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:2948	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:2948
ChemicalBook	CB2170327	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB2170327
eMolecules	533997	https://www.emolecules.com/cgi-bin/more?vid=533997
eMolecules	731311	https://www.emolecules.com/cgi-bin/more?vid=731311
MolPort	MolPort-000-745-914	https://www.molport.com/shop/molecule-link/MolPort-000-745-914
MolPort	MolPort-000-764-262	https://www.molport.com/shop/molecule-link/MolPort-000-764-262
Selleck Chemicals	Azathioprine(Azasan)	http://www.selleckchem.com/products/Azathioprine(Azasan).html
ZINC	ZINC000004258316	http://zinc15.docking.org/substances/ZINC000004258316

PubMed

Title	Date	PubMed
Thiopurine methyltransferase (TPMT) heterozygosity and enzyme activity as predictive tests for the development of azathioprine-related adverse events.	2005-04-15	15792824
Monozygotic twins concordant for intestinal Behçet's disease.	2005-04	15870978
[Adamantiades-Behcet's disease].	2005-04	15668761
Development of multiple malignancies after immunosuppression in a patient with Wegener's granulomatosis.	2005-04	15660233
Azathioprine-induced pancytopenia in a patient with pompholyx and deficiency of erythrocyte thiopurine methyltransferase.	2005-02-12	15705694
Severe cholestatic hepatitis caused by azathioprine.	2005	15803861
Sinusoidal dilatation: a rare side effect of azathioprine.	2004-12	15547102
[Disseminated intravascular coagulation, perimyocarditis and bilateral pleural empyema in adult Still's disease].	2004-11-19	15543470
Immunomodulatory therapy for Crohn's disease resulting in acute liver failure.	2004-11	15626912
Lack of association between the ITPA 94C>A polymorphism and adverse effects from azathioprine.	2004-11	15564886
Increased incidence of azathioprine-induced pancreatitis in Crohn's disease compared with other diseases.	2004-10-15	15479355
[New horizons in heart transplantation].	2004-10	15651155
Colitic cancer developed after introduction of azathioprine.	2004-10	15573934
Genetic determinants of the pre- and post-azathioprine therapy thiopurine methyltransferase activity phenotype.	2004-10	15571267
Mutation in the ITPA gene predicts intolerance to azathioprine.	2004-10	15571265
[Panzytopenia from combination therapy with azathioprin and allopurinol].	2004-10	15517303
The impact of thiopurine S-methyltransferase polymorphisms on azathioprine dose 1 year after renal transplantation.	2004-10	15349717
Cost-effectiveness of thiopurine methyltransferase genotype screening in patients about to commence azathioprine therapy for treatment of inflammatory bowel disease.	2004-09-15	15352906
[Life-threatening adverse effects of pharmacologic antihyperuricemic therapy].	2004-09	15493119
Hypersensitivity reaction to azathioprine in a patient with ulcerative colitis. Infrequent manifestations.	2004-09	15472540
[Azathioprine-associated myelodysplastic syndrome with cytogenetic aberrations].	2004-05-28	15170581
A case of refractory anemia with 17p- syndrome following azathioprine treatment for heart transplantation.	2004-04	14961032
Adverse drug reactions to azathioprine therapy are associated with polymorphism in the gene encoding inosine triphosphate pyrophosphatase (ITPase).	2004-03	15167706
Effect of antimetabolite immunosuppressants on Flaviviridae, including hepatitis C virus.	2004-02-27	15084936
Use of infliximab, an anti-tumor necrosis alpha antibody, for inflammatory dermatoses.	2004-02-20	14973643
New approaches to the treatment of pemphigus.	2004-01	14870992
Fibrosing cholestatic hepatitis in renal transplant recipient with CMV infection: a case report.	2004	15783120
Potential involvement of the immune system in the development of endometriosis.	2003-12-02	14651748
[Immunomodulation in penetrating keratoplasty. Current status and perspectives].	2003-12	14704816
Colchicine-induced myopathy in a teenager with familial Mediterranean fever.	2003-12	14632592
Differential diagnosis of high serum creatine kinase levels in systemic lupus erythematosus.	2003-11	12739036
Systemic lupus erythematosus with presentation as vertigo and vertical nystagmus: report of one case.	2003-10-03	14521022
Azathioprine and prednisone combination therapy in refractory coeliac disease.	2003-09-01	12950421
Veno-occlusive disease (VOD) in Crohn's disease (CD) treated with azathioprine.	2003-08	12924643
Microemulsified cyclosporine-based immunosuppression for the prevention of acute renal allograft rejection in unrelated dogs: preliminary experimental study.	2003-06-05	12784197
Severe villus atrophy and chronic malabsorption induced by azathioprine.	2003-06	12806628
Gastrointestinal cytomegalovirus infection in collagen diseases.	2003-04	12880302
CD28-dependent Rac1 activation is the molecular target of azathioprine in primary human CD4+ T lymphocytes.	2003-04	12697733
[Incidence and characteristics of tuberculosis in patients with autoimmune rheumatic diseases].	2003-04	12681200
Azathioprine-induced fatal macrocytic anemia in rabbits.	2003-02-21	12593539
Is thiopurine methyltransferase genetic polymorphism a major factor for withdrawal of azathioprine in rheumatoid arthritis patients?	2003-01	12509611
Hyperprolactinemia caused by azathioprine.	2003-01	12488716
Visual symptoms in patients on cyclophosphamide may herald sight threatening disease.	2003-01	12488280
[Treatment of rheumatoid arthritis].	2003	15098369
Low-dose azathioprine is effective and safe for maintenance of remission in patients with ulcerative colitis.	2003	14505127
[The influence of azathioprine on the osteogenesis of the limbs].	2003	12829883
[Cutaneous complications in idiopathic inflammatory bowel disease].	2002-11-08	12532909
[IgA nephropathy (Berger's disease) in children].	1992-12	1492913
[Hepatic hemangiomas and rheumatoid arthritis in patients treated with azathioprine].	1992-10	1420764
Enalapril and reversible acute renal failure.	1992	1315003

Patents

Sample Use Guides

In Vivo Use Guide

Rheumatoid Arthritis: is given on a daily basis. The initial dose should be approximately 1.0 mg/kg (50 to 100 mg) given as a single dose or on a twice-daily schedule. The dose may be increased, beginning at 6 to 8 weeks and thereafter by steps at 4-week intervals, if there are no serious toxicities and if initial response is unsatisfactory. Dose increments should be 0.5 mg/kg daily, up to a maximum dose of 2.5 mg/kg per day. Therapeutic response occurs after several weeks of treatment, usually 6 to 8 an adequate trial should be a minimum of 12 weeks.

Route of Administration: Oral

In Vitro Use Guide

Unknown

Substance Class	Chemical Created by `admin` on `Mon Mar 31 17:49:29 GMT 2025` Edited by `admin` on `Mon Mar 31 17:49:29 GMT 2025`
Record UNII	MRK240IY2L
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

Azasan

Preferred Name

English

Azathioprine

Official Name

English

Azathioprine [MART.]

Common Name

English

BW-57-322

Code

English

Azathioprine [HSDB]

Common Name

English

Azathioprine [MI]

Common Name

English

Azathioprinum [WHO-IP LATIN]

Common Name

English

1H-Purine, 6-((1-methyl-4-nitro-1H-imidazol-5-yl)thio)

Systematic Name

English

Azathioprine [VANDF]

Common Name

English

NSC-39084

Code

English

Azathioprine [JAN]

Common Name

English

Azathioprine [EP IMPURITY]

Common Name

English

Azathioprine [USP-RS]

Common Name

English

Azathioprine [IARC]

Common Name

English

Azathioprine [ORANGE BOOK]

Common Name

English

IMURAN

Brand Name

English

6-[(1-Methyl-4-nitroimidazol-5-yl)thio]purine

Systematic Name

English

Azathioprine [INN]

Common Name

English

6-((1-Methyl-4-nitroimidazol-5-yl)thio)purine6-((1-methyl-4-nitro-1H-imidazol-5-yl)thio)-1H-purine

Systematic Name

English

Azathioprine [USP MONOGRAPH]

Common Name

English

Azathioprine [USAN]

Common Name

English

Azathioprine [WHO-IP]

Common Name

English

Azathioprine [WHO-DD]

Common Name

English

Azathioprine [EP MONOGRAPH]

Common Name

English

Classification Tree Code System Code

LIVERTOX

NBK548332