Azathioprine

Summary

Azathioprine (CHEMBL1542) is an approved small-molecule antineoplastic agent (ATC L04AX01); indicated across 41 conditions including rheumatoid arthritis and immune system disorder; with CIViC clinical evidence for 1 variant-indication association (e.g. NUDT15 Inactivating Mutation in childhood acute lymphocytic leukemia).

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: L04AX01
• Indications: 41 conditions
• Clinical trials: 118
• Precision-oncology evidence (CIViC): 1 variant–indication association
• Chemistry: 277.27 Da · C9H7N7O2S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1542
Name	Azathioprine
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	2265
ChEBI	CHEBI:2948
ATC	L04AX01
Molecular formula	C9H7N7O2S
Molecular weight	277.27
InChIKey	LMEKQMALGUDUQG-UHFFFAOYSA-N

SMILES: CN1C=NC(=C1SC2=NC=NC3=C2NC=N3)[N+](=O)[O-]

IUPAC name: 6-(3-methyl-5-nitroimidazol-4-yl)sulfanyl-7H-purine

ChEBI definition: A thiopurine that is 6-mercaptopurine in which the mercapto hydrogen is replaced by a 1-methyl-4-nitroimidazol-5-yl group. It is a prodrug for mercaptopurine and is used as an immunosuppressant, prescribed for the treatment of inflammatory conditions and after organ transplantation and also for treatment of Crohn’s didease and MS.

Pharmacological roles (ChEBI): antineoplastic agent, immunosuppressive agent, prodrug, carcinogenic agent, DNA synthesis inhibitor, hepatotoxic agent.

Other ChEBI roles (chemical / environmental): antimetabolite.

Also known as: Azamune, Azapress, Azasan, Azathioprine, Azathioprinum, Azatioprina, Berkaprine, Immunoprin 50, Imuran, Jayempi, Kentaprine, NSC-39084

Parent form; salt/anhydrous children: CHEMBL1200400, CHEMBL3785814, CHEMBL3785780

Patent coverage: 30,016 distinct patent families (120,036 SureChEMBL compound mentions), from 4 matched compound structure(s). One matched structure accounts for 118,682 (99%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Broader ChEMBL bioactivity targets: 15 (assay-derived). Sample: Tyrosyl-DNA phosphodiesterase 1, Microtubule-associated protein tau, Survival motor neuron protein, Prelamin-A/C, RecQ-like DNA helicase BLM, 4’-phosphopantetheinyl transferase ffp, Ferritin light chain, Geminin, Peripheral myelin protein 22, Progesterone receptor.

Bioactivity

ChEMBL activities: 21 potent at pChembl ≥ 5 of 30 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
BLM	6.7	Potency	199.5	nM	CHEMBL_ACT_4745806
BLM	6.7	Potency	199.5	nM	CHEMBL_ACT_4917811
HBB	6.5	Potency	316.2	nM	CHEMBL_ACT_3770476
LMNA	6.4	Potency	398.1	nM	CHEMBL_ACT_3624074
HBB	6.3	Potency	501.2	nM	CHEMBL_ACT_4537488
TP53	6.1	Potency	794.3	nM	CHEMBL_ACT_4862311
P02791	6.05	Potency	891.3	nM	CHEMBL_ACT_4471743
SMN1	5.8	Potency	1585	nM	CHEMBL_ACT_3881225
HBB	5.8	Potency	1585	nM	CHEMBL_ACT_4537515
HBB	5.8	Potency	1585	nM	CHEMBL_ACT_4880876
GMNN	5.75	Potency	1778	nM	CHEMBL_ACT_5061240
HBB	5.7	Potency	1995	nM	CHEMBL_ACT_4107387
HBB	5.7	Potency	1995	nM	CHEMBL_ACT_4881035
HBB	5.6	Potency	2512	nM	CHEMBL_ACT_3765591
TP53	5.5	Potency	3162	nM	CHEMBL_ACT_4877800
CYP3A4	5.4	Potency	3981	nM	CHEMBL_ACT_4981665
CYP3A4	5.4	Potency	3981	nM	CHEMBL_ACT_5050692
HBB	5.3	Potency	5012	nM	CHEMBL_ACT_4881011
PGR	5.1	AC50	8000	nM	CHEMBL_ACT_25192827
SMN1	5.05	Potency	8912	nM	CHEMBL_ACT_3874410
P08482	5	Potency	10000	nM	CHEMBL_ACT_4853785

Target pathways

No target-pathway data for this drug (no mapped target genes).

Indications & clinical

Indications

41 indications (3 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
rheumatoid arthritis	4	MONDO:0008383	EFO:0000685
immune system disorder	4	MONDO:0005046	EFO:0000540
myasthenia gravis	3	MONDO:0009688	EFO:0004991
vasculitis	3	MONDO:0018882	EFO:0006803
Crohn disease	3	MONDO:0005011	EFO:0000384
ulcerative colitis	3	MONDO:0005101	EFO:0000729
hepatocellular carcinoma	3	MONDO:0007256	EFO:0000182
cardiomyopathy	3	MONDO:0004994	EFO:0000318
chronic kidney disease	3	MONDO:0005300	EFO:0003884
IgA glomerulonephritis	3	MONDO:0005342	EFO:0004194
neuromyelitis optica	3	MONDO:0019100	EFO:0004256
anti-neutrophil antibody associated vasculitis	3	MONDO:0005435	EFO:0004826
granulomatosis with polyangiitis	3	MONDO:0012105	EFO:0005297
lupus nephritis	3	MONDO:0005556	EFO:0005761
eosinophilic granulomatosis with polyangiitis	3	MONDO:0015943	EFO:0007208
microscopic polyangiitis	3	MONDO:0019124	EFO:1000784
Takayasu arteritis	3	MONDO:0017991	EFO:1001857
thrombocytopenia	3	MONDO:0002049	HP:0001873
pulmonary fibrosis	3	MONDO:0002771	EFO:0009448
encephalomyelitis	3	MONDO:0005156	EFO:0001423
systemic lupus erythematosus	3	MONDO:0007915	MONDO:0007915
kidney disorder	3	MONDO:0005240	EFO:0003086
idiopathic pulmonary fibrosis	2	MONDO:0800504	EFO:0000768
lung disorder	2	MONDO:0005275	EFO:0003818
interstitial lung disease	2	MONDO:0015925	EFO:0004244
gout	2	MONDO:0005393	EFO:0004274
pemphigus vulgaris	2	MONDO:0008219	EFO:0004719
autoimmune hepatitis	2	MONDO:0016264	EFO:0005676
bullous pemphigoid	2	MONDO:0019082	EFO:0007187
infertility disorder	2	MONDO:0005047	EFO:0000545
acute myeloid leukemia	2	MONDO:0018874	EFO:0000222
pemphigus	2	MONDO:0006594	EFO:1000749
sickle cell disease	2	MONDO:0011382	MONDO:0011382
acute lymphoblastic leukemia	2	MONDO:0004967	EFO:0000220
inflammatory bowel disease	1	MONDO:0005265	EFO:0003767
urticaria	1	MONDO:0005492	EFO:0005531
myelodysplastic syndrome	1	MONDO:0018881	EFO:0000198
mucopolysaccharidosis	1	MONDO:0019249	MONDO:0019249
dermatitis	0	MONDO:0002406	MONDO:0002406

2 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 118.

Phase distribution

Phase	Trials
PHASE3	33
PHASE4	32
Not specified	24
PHASE2	18
PHASE2/PHASE3	5
PHASE1	3
EARLY_PHASE1	2
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02081755	PHASE4	ENROLLING_BY_INVITATION	Safety and Efficacy of Everolimus Treatment in Liver Transplantation for Liver Cancer
NCT04654988	PHASE4	RECRUITING	Study to Evaluate the Efficacy of Immunosuppression in Myocarditis or Inflammatory Cardiomyopathy.
NCT05813860	PHASE4	NOT_YET_RECRUITING	HLADQA1*05 Genotype and the Efficacy of Treatment With Infliximab in Chinese Population Crohn’s Disease
NCT05965284	PHASE4	RECRUITING	Efficacy and Safety for Telitacicept in the Remission Maintenance Treatment of ANCA-associated Vasculitis (TTCAZAREM)
NCT07235904	PHASE4	RECRUITING	Efficacy of Top-down Therapy With Mirikizumab Versus Standard of Care With Azathioprine in Patients With Newly Diagnosed Moderate-to-severe Ulcerative Colitis
NCT07352566	PHASE4	NOT_YET_RECRUITING	Utilization of a Microdevice for Psoriasis and Atopic Dermatitis
NCT00128895	PHASE4	TERMINATED	Prevention of Relapses in Proteinase 3 (PR3)-Anti-neutrophil Cytoplasmic Antibodies (ANCA)-Associated Vasculitis
NCT00307671	PHASE4	COMPLETED	Treatment of Necrotizing Vasculitides for Patients Older Than 65 Years
NCT00321906	PHASE4	COMPLETED	Comparison of Sirolimus and Azathioprine in Lung Transplantation
NCT00399399	PHASE4	UNKNOWN	CHUSPAN SCS BP Treatment of Churg-Strauss Syndrome Without Poor-Prognosis Factors
NCT00400075	PHASE4	UNKNOWN	CHUSPAN PAN BP Treatment of Polyarteritis Nodosa and Microscopic Polyangiitis Without Poor-Prognosis Factors
NCT00494741	PHASE4	COMPLETED	MMF vs. AZA for Kidney Transplantation
NCT00554710	PHASE4	COMPLETED	Top Down Versus Step Up Strategies in Crohn’s Disease
NCT00866684	PHASE4	TERMINATED	Prevention of Skin Cancer in High Risk Patients After Conversion to a Sirolimus-based Immunosuppressive Protocol
NCT01112215	PHASE4	COMPLETED	Enteric-coated Mycophenolate Sodium Versus Azathioprine for the Extra-renal Lupus Manifestations
NCT01880307	PHASE4	TERMINATED	Infliximab Top-down in Pediatric Crohn
NCT02177071	PHASE4	COMPLETED	A proSpective Randomized Controlled Trial comParing infliximAb-antimetabolites Combination Therapy to Anti-metabolites monotheRapy and Infliximab monothErapy in Crohn’s Disease Patients in Sustained Steroid-free Remission on Combination Therapy
NCT02281799	PHASE4	WITHDRAWN	Thiopurine Induced Pancreatitis in IBD Patients
NCT02425852	PHASE4	COMPLETED	A Randomized, Multicenter Open Label Study Comparing Early Administration of Azathioprine Plus IFX to Steroids Plus Azathioprine for Acute Severe Colitis
NCT02463331	PHASE4	COMPLETED	Possible Role of Chloroquine to Induce a Complete Remission in the Treatment of Autoimmune Hepatitis: a Randomized Trial
NCT02517684	PHASE4	COMPLETED	Top-down Infliximab Study in Kids With Crohn’s Disease
NCT02579733	PHASE4	TERMINATED	Azathioprine Based on Endoscopy After Clinical Remission in Moderate to Severe Ulcerative Colitis
NCT02645565	PHASE4	COMPLETED	Comparison of Low Dose Versus High Dose Cyclophosphamide as Induction Therapy in the Treatment of Lupus Nephritis
NCT02852694	PHASE4	COMPLETED	Reduce Risk for Crohn’s Disease Patients
NCT02900443	PHASE4	UNKNOWN	Mycophenolate Mofetil Versus Azathioprine in Treatment Naive Autoimmune Hepatitis
NCT03151525	PHASE4	UNKNOWN	Two Therapeutic Strategies for the Maintenance of Remission in Patients With Ulcerative Colitis
NCT03229746	PHASE4	COMPLETED	Reposition of Second Line Treatment in Chronic Immune Thrombocytopenia
NCT03449758	PHASE4	COMPLETED	Effect of Sarilumab on Patient-reported Outcomes in Patients With Active Rheumatoid Arthritis
NCT04773392	PHASE4	TERMINATED	Simplified IMmunosuppressive Protocol Utilizing Low Dose EnvarsusXR
NCT04933292	PHASE4	UNKNOWN	A Randomised Clinical Trial Assessing the Efficacy and Safety of Mycophenolate Mofetil Versus Azathioprine for Induction of Remission in Treatment Primary Biliary Cholangitis-Autoimmune Hepatitis Overlap Syndrome
NCT05861297	PHASE4	UNKNOWN	Immune Thrombocytopenia Management in Adults
NCT05896605	PHASE4	COMPLETED	Monitoring of Azathioprine Metabolite Concentrations and Cytokine Levels in Neuromyelitis Optica Spectrum Disorder
NCT03414502	PHASE3	RECRUITING	Treatment of Rheumatoid Arthritis With DMARDs: Predictors of Response
NCT05030155	PHASE3	ACTIVE_NOT_RECRUITING	Study of Mepolizumab-based Regimen Compared to Conventional Therapeutic Strategy in Patients With Eosinophilic Granulomatosis With Polyangiitis (E-merge)
NCT05349006	PHASE3	RECRUITING	Azathioprine in MOGAD
NCT05646992	PHASE2/PHASE3	RECRUITING	Uterus Transplantation to Treat Infertility
NCT06650124	PHASE2/PHASE3	NOT_YET_RECRUITING	Induction of Remission in Autoimmune Hepatitis With Azathioprine vs. MMF
NCT07168161	PHASE3	RECRUITING	BDB-001 Phase III Trial in ANCA-Associated Vasculitis
NCT00052039	PHASE3	TERMINATED	A Randomized, Double-Blind, Three-Arm, Phase 3b Study Comparing the Safety and Efficacy of Interferon Gamma-1b With Azathioprine, and Azathioprine Alone in Patients With IPF Receiving Prednisone
NCT00098111	PHASE3	TERMINATED	Imuran (Azathioprine) Dose-Ranging Study in Crohn’s Disease

Clinical evidence (CIViC)

Variant × indication × effect (1 predictive associations from 1 curated evidence items):

Variant	Indication	Effect	Therapy	Level	CIViC
NUDT15 Inactivating Mutation	Childhood Acute Lymphocytic Leukemia	Adverse Response	Azathioprine + Mercaptopurine + Thioguanine	CIViC B	EID7794

Pharmacology

Pharmacogenomics

PharmGKB dosing guidelines (4) — CPIC / DPWG genotype-guided dosing for this drug (drug × pharmacogene):

Guideline	Source	Gene(s)	Dosing	Recommendation
Annotation of CPIC Guideline for azathioprine and NUDT15, TPMT	CPIC	NUDT15;TPMT	yes	yes
Annotation of DPWG Guideline for azathioprine and TPMT	DPWG	TPMT	yes	yes
Annotation of DPWG Guideline for azathioprine and NUDT15	DPWG	NUDT15	yes	yes
Annotation of RNPGx Guideline for azathioprine and TPMT	RNPGx	TPMT	yes	yes

PharmGKB also curates 21 clinical and 215 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

Related molecules

Related molecules

No competitor molecules sharing a primary target (ChEMBL phase ≥2 or PubChem drug-class).