Sulfasalazine

Summary

Sulfasalazine (CHEMBL421) is an approved small-molecule non-steroidal anti-inflammatory drug (ATC A07EC01) targeting SLC46A1; indicated across 15 conditions including rheumatoid arthritis and juvenile idiopathic arthritis.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: A07EC01
• Targets: 1 (SLC46A1)
• Indications: 15 conditions
• Clinical trials: 58
• Chemistry: 398.4 Da · C18H14N4O5S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL421
Name	Sulfasalazine
Type	Small molecule
Max phase	4
FDA approved	no
PubChem CID	5339
ChEBI	CHEBI:9334
ATC	A07EC01
Molecular formula	C18H14N4O5S
Molecular weight	398.4
InChIKey	NCEXYHBECQHGNR-UHFFFAOYSA-N

SMILES: C1=CC=NC(=C1)NS(=O)(=O)C2=CC=C(C=C2)N=NC3=CC(=C(C=C3)O)C(=O)O

IUPAC name: 2-hydroxy-5-[[4-(pyridin-2-ylsulfamoyl)phenyl]diazenyl]benzoic acid

ChEBI definition: An azobenzene consisting of diphenyldiazene having a carboxy substituent at the 4-position, a hydroxy substituent at the 3-position and a 2-pyridylaminosulphonyl substituent at the 4’-position.

Pharmacological roles (ChEBI): non-steroidal anti-inflammatory drug, antiinfective agent, gastrointestinal drug, EC 2.5.1.18 (glutathione transferase) inhibitor, drug allergen, ferroptosis inducer.

Also known as: Azulfidine, Azulfidine en-tabs, Benzosulfa, Colizine, NSC-203730, NSC-667219, S.a.s.-500, Salazopyrin, Salazopyrin e.c., Salazopyrin-en, Salazosulfapyridine, Salicylazosulfapyridine

Parent form; salt/anhydrous children: CHEMBL2311115, CHEMBL3765414

Patent coverage: 18,373 distinct patent families (73,629 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 73,628 (100%) 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

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
SLC46A1	Proton-coupled folate transporter	Inhibition	4.2	2.7%	Q96NT5

Broader ChEMBL bioactivity targets: 29 (assay-derived). Sample: Cystine/glutamate transporter, Microtubule-associated protein tau, Prelamin-A/C, 15-hydroxyprostaglandin dehydrogenase [NAD(+)], Solute carrier organic anion transporter family member 1B1, Solute carrier organic anion transporter family member 1B3, Solute carrier organic anion transporter family member 2B1, ATP-binding cassette sub-family C member 4, Thromboxane-A synthase, Thyrotropin receptor, Carbonic anhydrase 2, Menin/Histone-lysine N-methyltransferase MLL, Nuclear factor NF-kappa-B complex, Bifunctional purine biosynthesis protein ATIC, Carbonic anhydrase 1, Aldo-keto reductase family 1 member B1, Histamine H3 receptor, Androgen receptor, Interstitial collagenase, Aldehyde dehydrogenase 1A1.

Bioactivity

ChEMBL activities: 24 potent at pChembl ≥ 5 of 45 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
LMNA	7.5	Potency	31.6	nM	CHEMBL_ACT_3667663
SLC7A11	6.8	IC50	160	nM	CHEMBL_ACT_18950385
HIF1A	6.65	Potency	223.9	nM	CHEMBL_ACT_3769526
BLVRB	6.36	Kd	440	nM	CHEMBL_ACT_24380453
BLVRB	6.36	Kd	436.5	nM	CHEMBL_ACT_24380454
ABCG2	6.34	IC50	460	nM	CHEMBL_ACT_24777414
SLCO1B1	6.28	Ki	530	nM	CHEMBL_ACT_12088867
SLCO1B1	6.25	IC50	560	nM	CHEMBL_ACT_12088868
ABCB1	6.04	EC50	916	nM	CHEMBL_ACT_22472133
ABCC4	5.82	IC50	1500	nM	CHEMBL_ACT_18130902
TSHR	5.8	Potency	1585	nM	CHEMBL_ACT_3937295
TSHR	5.8	Potency	1585	nM	CHEMBL_ACT_4739410
SLCO2B1	5.52	Ki	3000	nM	CHEMBL_ACT_12088863
SLCO2B1	5.52	IC50	3000	nM	CHEMBL_ACT_12088864
CA1	5.52	IC50	3040	nM	CHEMBL_ACT_2259029
CA2	5.35	IC50	4490	nM	CHEMBL_ACT_2259038
MAPK1	5.2	IC50	6332	nM	CHEMBL_ACT_7818578
CA1	5.16	Ki	6870	nM	CHEMBL_ACT_2259048
HRH3	5.14	AC50	7200	nM	CHEMBL_ACT_25200439
K9N7C7	5.12	Kd	7600	nM	CHEMBL_ACT_19212048
CA2	5.06	Ki	8720	nM	CHEMBL_ACT_2259058
SLC10A1	5.02	IC50	9600	nM	CHEMBL_ACT_19242118
SLC10A1	5.02	IC50	9600	nM	CHEMBL_ACT_24868561
NFKB1	5	IC50	10000	nM	CHEMBL_ACT_25878329

Target pathways

Aggregated over 1 target gene(s): SLC46A1.

Top Reactome pathways

3 total, by targets touching each:

Pathway	Targets	Genes
Metabolism of folate and pterines	1	SLC46A1
Iron uptake and transport	1	SLC46A1
Heme signaling	1	SLC46A1

Dominant GO biological processes

GO term	Targets
intracellular iron ion homeostasis	1
folic acid transport	1
heme metabolic process	1
tetrahydrofolate biosynthetic process	1
folic acid metabolic process	1
transmembrane transport	1
intestinal folate absorption	1
folate transmembrane transport	1
proton transmembrane transport	1
folate import across plasma membrane	1
heme transport	1
methotrexate transport	1

Indications & clinical

Indications

3 approved indications. FDA phase 4, plus an anticancer drug’s labelled cancer uses (which ChEMBL often logs at phase 3).

Indication	Phase	MONDO	EFO
rheumatoid arthritis	4	MONDO:0008383	EFO:0000685
juvenile idiopathic arthritis	4	MONDO:0011429	EFO:0002609
ulcerative colitis	4	MONDO:0005101	EFO:0000729

9 diseases in clinical trials (phase 1–3, investigational — not approved indications). Highest ChEMBL trial phase per disease; a non-cancer approved use is occasionally logged at phase 3 here.

Disease (in trials)	Phase	MONDO	EFO
psoriatic arthritis	3	MONDO:0011849	EFO:0003778
ankylosing spondylitis	2	MONDO:0005306	EFO:0003898
peripheral nervous system disorder	2	MONDO:0003620	EFO:0004149
sclerosing cholangitis	2	MONDO:0018646	EFO:0004268
glioblastoma	1	MONDO:0018177	EFO:0000519
intestinal obstruction	1	MONDO:0004565	MONDO:0004565
pulmonary arterial hypertension	1	MONDO:0015924	EFO:0001361
acute myeloid leukemia	1	MONDO:0018874	EFO:0000222
paraganglioma	1	MONDO:0000448	EFO:1000453

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

Clinical trials

Total trials: 58.

Phase distribution

Phase	Trials
PHASE4	17
PHASE3	11
PHASE1	9
Not specified	9
PHASE2	8
PHASE1/PHASE2	3
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02714634	PHASE4	RECRUITING	Clinical Trial Evaluating Methotrexate or Leflunomide + Targeted Therapy Versus Methotrexate or Leflunomide + Sulfasalazine + Hydroxychloroquine in Patients With Rheumatoid Arthritis and Insufficient Response to Methotrexate or Leflunomide
NCT00247962	PHASE4	COMPLETED	Study Evaluating Etanercept and Sulphasalazine in Ankylosing Spondylitis
NCT00259610	PHASE4	COMPLETED	Treatment of Early Aggressive Rheumatoid Arthritis (TEAR)
NCT00637780	PHASE4	TERMINATED	Study To Determine The Pharmacokinetics Of Sulfasalazine In Children With Juvenile Idiopathic Arthritis
NCT00908089	PHASE4	UNKNOWN	TNF-blocking Therapy in Combination With Disease-modifying Antirheumatic Drugs in Early Rheumatoid Arthritis
NCT01172639	PHASE4	COMPLETED	Effectiveness in Daily Practice of Different Treatment Strategies for Early Rheumatoid Arthritis.
NCT02374021	PHASE4	COMPLETED	Treatments Against RA and Effect on FDG-PET/CT
NCT02433184	PHASE4	COMPLETED	Very Early Versus Delayed Etanercept in Patients With RA
NCT02451748	PHASE4	COMPLETED	IL-7 and IL-7R Expression in RA Patients With Active vs. Inactive Disease Treated With DMARD or CIMZIA
NCT02466581	PHASE4	UNKNOWN	Dose Reduction for Early Rheumatoid Arthritis Patients With Low Disease Activity
NCT02638896	PHASE4	UNKNOWN	Dose Reduction of Etanercept in Patients With Ankylosing Spondylitis
NCT03254589	PHASE4	COMPLETED	Methotrexate, Blood Pressure and Arterial Function in Rheumatoid Arthritis
NCT03449758	PHASE4	COMPLETED	Effect of Sarilumab on Patient-reported Outcomes in Patients With Active Rheumatoid Arthritis
NCT03739853	PHASE4	COMPLETED	Severe Psoriatic Arthritis - Early intervEntion to Control Disease: the SPEED Trial
NCT03797872	PHASE4	COMPLETED	Psoriatic Oligoarthritis Intervention With Symptomatic thErapy
NCT03813771	PHASE4	UNKNOWN	Targeted Treatment Early With Etanercept + Methotrexate vs.T2T Care for DMARD-naïve Early RA Patients Based on naïve T-cell Stratification
NCT04077957	PHASE4	UNKNOWN	Treat-to-target Strategy in Ankylosing Spondylitis Using Etanercept and Conventional Synthetic DMARDs
NCT03414502	PHASE3	RECRUITING	Treatment of Rheumatoid Arthritis With DMARDs: Predictors of Response
NCT06060301	PHASE3	ACTIVE_NOT_RECRUITING	Topical Sulfasalazine and Oral Lichen Planus
NCT06134388	PHASE3	RECRUITING	Sulfasalazine in Patients With Metastatic Colorectal Cancer
NCT00889694	PHASE2/PHASE3	UNKNOWN	Clinical Study of Tripterygium Capsule to Treat Early Ankylosing Spondylitis
NCT01198145	PHASE3	COMPLETED	Sulfasalazine in Preventing Acute Diarrhea in Patients With Cancer Who Are Undergoing Pelvic Radiation Therapy
NCT01709578	PHASE3	COMPLETED	To Evaluate The Effect Of SAR153191 (REGN88) Added To Other RA Drugs In Patients With RA Who Are Not Responding To Or Intolerant Of Anti-TNF Therapy (SARIL-RA-TARGET)
NCT01768572	PHASE3	COMPLETED	To Evaluate The Safety of SAR153191 (REGN88) and Tocilizumab Added to Other RA Drugs in Patients With RA Who Are Not Responding to or Intolerant of Anti-TNF Therapy (SARIL-RA-ASCERTAIN)
NCT01941095	PHASE3	COMPLETED	A Study of Subcutaneous Tocilizumab as Monotherapy and/or in Combination With Non-Biologic Disease Modifying Anti-Rheumatic Drugs (DMARDs) in Participants With Rheumatoid Arthritis
NCT02057250	PHASE3	COMPLETED	To Evaluate Sarilumab - SAR153191 (REGN88) - Auto-injector Device In Patients With Rheumatoid Arthritis
NCT02373202	PHASE3	COMPLETED	A Study Assessing the Safety and Efficacy of Sarilumab Added to Non-MTX DMARDs or as Monotherapy in Japanese Patients With Active Rheumatoid Arthritis (SARIL-RA-HARUKA)
NCT02930343	PHASE3	TERMINATED	Comparison of Disease Modifying Antirheumatic Drugs Therapy in Patients With RA Failing Methotrexate Monotherapy
NCT04610476	PHASE3	UNKNOWN	Impact of Tapering Immunosuppressants on Maintaining Minimal Disease Activity in Adult Subjects With Psoriatic Arthritis
NCT05580861	PHASE1/PHASE2	RECRUITING	Sulfasalazine in AML Treated by Intensive Chemotherapy: Elderly Patients-first Line Treatment
NCT05664464	PHASE1/PHASE2	RECRUITING	Glutamate Inhibitors in Glioblastoma
NCT05703425	PHASE2	RECRUITING	The Effect of Sulfasalazine on CRH Levels in Pregnant Women
NCT07138898	PHASE2	NOT_YET_RECRUITING	Immunosuppressant Management in Rheumatology Patients Undergoing Elective Total Shoulder Arthroplasty
NCT00844142	PHASE2	UNKNOWN	Enbrel-Sulfasalazin-Early-Axial Spondyloarthritis (AS)
NCT01667029	PHASE2	TERMINATED	Study of Sulfasalazine in Treating Painful Neuropathy
NCT02456363	PHASE2	UNKNOWN	Anti-Tumor Necrosis Factor Therapy In Patients With Ankylosing Spondylitis
NCT03561584	PHASE2	COMPLETED	Sulfasalazine for the Treatment of Primary Sclerosing Cholangitis
NCT03847311	PHASE2	COMPLETED	Sulfasalazine in Decreasing Opioids Requirements in Breast Cancer Patients
NCT04528056	PHASE1/PHASE2	UNKNOWN	Pilot Study of the Safety and Efficacy of Sulfasalazine in Pulmonary Arterial Hypertension
NCT06360068	PHASE2	UNKNOWN	A Prospective, Single Arm, Open Label, Proof of Concept Clinical Study of Sulfasalazine in the Treatment of Active Systemic Lupus Erythematosus
NCT01596764	PHASE1	COMPLETED	Effects of Methylnaltrexone in Comparison to Naloxone on Loperamide-induced Delay of the Oro-cecal, Whole-gut and Colon Transit Time.
NCT01596777	PHASE1	COMPLETED	Effects of 500 mg Immediate Release and Extended Release Methylnaltrexone on Loperamide-induced Delay of the Oro-cecal and Whole-gut Transit Time in Healthy Subjects
NCT02434861	PHASE1	COMPLETED	An Open Label, Single Dose, Three Part Study to Assess the Effects of Rolapitant (2 mg/mL IV Solution) on the Pharmacokinetics of Digoxin; Sulfasalazine; and the Cooperstown Cocktail (Midazolam, Omeprazole, Warfarin, Caffeine, and Dextromethorphan in Healthy Subjects
NCT03012763	PHASE1	COMPLETED	Oral Pharmacokinetics of Sulfasalazine, Paracetamol, Fexofenadine and Valsartan Using Different Administration Mediums
NCT03801733	PHASE1	COMPLETED	Drug-Drug Interaction Study of Vadadustat With Rosuvastatin, Sulfasalazine, Pravastatin, Atorvastatin and Simvastatin
NCT04205357	PHASE1	COMPLETED	Sulfasalazine and Stereotactic Radiosurgery for Recurrent Glioblastoma
NCT04268394	PHASE1	COMPLETED	A Study to Evaluate Potential Cytochrome P450 and Transporter Protein Interactions With CC-99677
NCT04720183	PHASE1	COMPLETED	Drug-drug Interaction Study with GLPG3970 and Sulfasalazine in Adult, Healthy Subjects
NCT05445440	PHASE1	COMPLETED	A Study to Assess the Effects of BMS-986371 on the Drug Levels of Methotrexate in the Presence and Absence of Sulfasalazine
NCT04725422	Not specified	RECRUITING	CHronic Nonbacterial Osteomyelitis International Registry
NCT06293378	Not specified	RECRUITING	Safety and Effectiveness of Sulfasalazine in the Treatment of Liver Fibrosis/Cirrhosis.
NCT00405275	Not specified	COMPLETED	Rheumatoid Arthritis: Comparison of Active Therapies in Patients With Active Disease Despite Methotrexate Therapy
NCT00554203	Not specified	COMPLETED	Sulfasalazine and Endothelial Function
NCT01312129	Not specified	COMPLETED	Effects of Sulfasalazine on BOLD Response to Alcohol Cues
NCT01577966	Not specified	COMPLETED	Pilot Study Effect of Sulfasalazine on Glutamate Levels by(Magnetic Resonance Spectroscopy)MRS in Patients With Glioma
NCT03440892	Not specified	UNKNOWN	Effects of Antirheumatic Treatment on Levels of Survivin in Rheumatoid Arthritis Patients
NCT03734627	Not specified	COMPLETED	Gastrointestinal Nutrient Transit and Enteroendocrine Function After Upper Gastrointestinal Surgery
NCT05051137	Not specified	COMPLETED	Real-World Emulation of the SWEFOT Trial

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

5 molecules share ≥1 primary target. Top 5 by shared-target count:

Molecule	Source	Status	Shared targets
METHOTREXATE	ChEMBL + PubChem	Phase 4 (approved)	SLC46A1
PEMETREXED	ChEMBL + PubChem	Phase 4 (approved)	SLC46A1
PRALATREXATE	ChEMBL + PubChem	Phase 4 (approved)	SLC46A1
RALTITREXED	ChEMBL	Phase 4 (approved)	SLC46A1
Indomethacin	PubChem	Approved	SLC46A1