Sulfasalazine

Details

Stereochemistry	ACHIRAL
Molecular Formula	C18H14N4O5S
Molecular Weight	398.393
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)C1=C(O)C=CC(=C1)\N=N\C2=CC=C(C=C2)S(=O)(=O)NC3=NC=CC=C3

InChI

InChIKey=NCEXYHBECQHGNR-QZQOTICOSA-N

InChI=1S/C18H14N4O5S/c23-16-9-6-13(11-15(16)18(24)25)21-20-12-4-7-14(8-5-12)28(26,27)22-17-3-1-2-10-19-17/h1-11,23H,(H,19,22)(H,24,25)/b21-20+

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB00795
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/007073s124lbl.pdf

Sulfasalazine is an anti-inflammatory indicated for the treatment of ulcerative colitis and rheumatoid arthritis. The mode of action of Sulfasalazine or its metabolites, 5-aminosalicylic acid (5-ASA) and sulfapyridine (SP), is still under investigation, but may be related to the anti-inflammatory and/or immunomodulatory properties that have been observed in animal and in vitromodels, to its affinity for connective tissue, and/or to the relatively high concentration it reaches in serous fluids, the liver and intestinal walls, as demonstrated in autoradiographic studies in animals. In ulcerative colitis, clinical studies utilizing rectal administration of Sulfasalazine, SP and 5-ASA have indicated that the major therapeutic action may reside in the 5-ASA moiety. The relative contribution of the parent drug and the major metabolites in rheumatoid arthritis is unknown. Sulfasalazine is used for the treatment of Crohn's disease and rheumatoid arthritis as a second-line agent. Sulfasalazine is marketed under the trade name Azulfidine among others.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Thromboxane-A synthase 21 Target ID: CHEMBL1835 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6135423	Inhibitor 8504	0.9 mM [IC50]
Cyclooxygenase-2 201 Target ID: CHEMBL230 Sources: http://www.drugbank.ca/drugs/DB00795	Inhibitor 8504
Cyclooxygenase-1 131 Target ID: CHEMBL221 Sources: http://www.drugbank.ca/drugs/DB00795	Inhibitor 8504
Arachidonate 5-lipoxygenase 52 Target ID: CHEMBL215 Sources: http://www.drugbank.ca/drugs/DB00795 \| https://www.ncbi.nlm.nih.gov/pubmed/2882965	Inhibitor 8504	293.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Ulcerative colitis 125 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/007073s124lbl.pdf	Primary		Approved 8583	AZULFIDINE Approved Use AZULFIDINE EN-tabs Tablets are indicated: a) in the treatment of mild to moderate ulcerative colitis, and as adjunctive therapy in severe ulcerative colitis; b) for the prolongation of the remission period between acute attacks of ulcerative colitis; c) in the treatment of patients with rheumatoid arthritis who have responded inadequately to salicylates or other nonsteroidal anti-inflammatory drugs (e.g., an insufficient therapeutic response to, or intolerance of, an adequate trial of full doses of one or more nonsteroidal anti-inflammatory drugs); and in the treatment of pediatric patients with polyarticular-course 1 juvenile rheumatoid arthritis who have responded inadequately to salicylates or other nonsteroidal antiinflammatory drugs. Launch Date 1950
Rheumatoid arthritis 320 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/007073s124lbl.pdf	Primary		Approved 8583	AZULFIDINE Approved Use AZULFIDINE EN-tabs Tablets are indicated: a) in the treatment of mild to moderate ulcerative colitis, and as adjunctive therapy in severe ulcerative colitis; b) for the prolongation of the remission period between acute attacks of ulcerative colitis; c) in the treatment of patients with rheumatoid arthritis who have responded inadequately to salicylates or other nonsteroidal anti-inflammatory drugs (e.g., an insufficient therapeutic response to, or intolerance of, an adequate trial of full doses of one or more nonsteroidal anti-inflammatory drugs); and in the treatment of pediatric patients with polyarticular-course 1 juvenile rheumatoid arthritis who have responded inadequately to salicylates or other nonsteroidal antiinflammatory drugs. Launch Date 1950

C_max

Value	Dose	Co-administered	Analyte	Population
12.9 μg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/1975737	2 g single, oral dose: 2 g route of administration: Oral experiment type: SINGLE co-administered:		SULFASALAZINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
27.4 μM × h REVIEW http://publications.iarc.fr/_publications/media/download/3250/cfef4a8f2e15aac3bf202aebfdc5ca409612ab71.pdf	6.5 mmol single, rectal dose: 6.5 mmol route of administration: Rectal experiment type: SINGLE co-administered:		SULFASALAZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
98 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/1975737	2 g single, oral dose: 2 g route of administration: Oral experiment type: SINGLE co-administered:		SULFASALAZINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
7.6 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/007073s124lbl.pdf	unknown, intravenous		SULFASALAZINE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
3.6 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/1975737	2 g single, oral dose: 2 g route of administration: Oral experiment type: SINGLE co-administered:		SULFASALAZINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Doses

Dose	Population	Adverse events
25 g single, oral Overdose Dose: 25 g Route: oral Route: single Dose: 25 g Sources: https://pubmed.ncbi.nlm.nih.gov/1684211	unhealthy, 23 Health Status: unhealthy Age Group: 23 Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/1684211	Disc. AE: Headache, Dizziness... AEs leading to discontinuation/dose reduction: Headache Dizziness Sources: https://pubmed.ncbi.nlm.nih.gov/1684211
50 g single, oral Overdose Dose: 50 g Route: oral Route: single Dose: 50 g Sources: https://pubmed.ncbi.nlm.nih.gov/9656981	unhealthy, 26 Health Status: unhealthy Age Group: 26 Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/9656981	Disc. AE: Lactic acidosis, Seizures... AEs leading to discontinuation/dose reduction: Lactic acidosis (severe) Seizures Coagulopathy Hyperglycemia Ketosis Methemoglobinemia Sources: https://pubmed.ncbi.nlm.nih.gov/9656981
1 g 3 times / day multiple, oral Recommended Dose: 1 g, 3 times / day Route: oral Route: multiple Dose: 1 g, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11856080	unhealthy, 43 Health Status: unhealthy Age Group: 43 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/11856080	Disc. AE: Headache, Headache... AEs leading to discontinuation/dose reduction: Headache (severe, 16.7%) Headache (8.3%) Nausea (12.5%) Nausea (severe, 8.3%) Acute pancreatitis (4.2%) Abdominal pain (4.2%) Lethargy (4.2%) Depression (8.3%) Dizziness (severe, 4.2%) Rash (4.2%) Light headedness (4.2%) Sources: https://pubmed.ncbi.nlm.nih.gov/11856080
1 g 2 times / day multiple, oral Recommended Dose: 1 g, 2 times / day Route: oral Route: multiple Dose: 1 g, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9588731	unhealthy, 8.4 ±4.4 Health Status: unhealthy Age Group: 8.4 ±4.4 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/9588731	Disc. AE: Toxic reaction (NOS), Anorexia... AEs leading to discontinuation/dose reduction: Toxic reaction (NOS) (serious, 2.9%) Anorexia (serious, 2.9%) Nausea (serious, 2.9%) Abdominal discomfort (serious, 2.9%) Headache (serious, 2.9%) Fever (serious, 2.9%) Rash (serious, 2.9%) Lymphadenopathy cervical (serious, 2.9%) Leukopenia (5.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/9588731

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BCRP 910 OAT1 725 OAT3 747 OATP1B1 1079 OATP1B3 961 OATP2B1 157	BCRP 697 CYP 303

Drug as perpetrator

Target	Modality	Activity
BCRP 985	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/21440623/	yes [IC50 0.73 uM]
OAT3 749	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/21440623/	yes [IC50 3 uM]
OAT1 730	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/21440623/	yes [IC50 4.6 uM]
OATP1B1 1095	inhibitor 4027 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3361267/	yes [Inhibition 20 uM]
OATP1B3 970	inhibitor 4027 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3361267/	yes [Inhibition 20 uM]
OATP2B1 162	inhibitor 4027 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3361267/	yes [Inhibition 20 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP 303	substrate 4014 Sources: https://www.sciencedirect.com/science/article/pii/S0022354916304075	no
BCRP 697	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19252303/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:9334	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:9334
ChemicalBook	CB0181156	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB0181156
MolPort	MolPort-001-792-507	https://www.molport.com/shop/molecule-link/MolPort-001-792-507
Selleck Chemicals	Sulfasalazine(Azulfidine)	http://www.selleckchem.com/products/Sulfasalazine(Azulfidine).html
ZINC	ZINC000003831490	http://zinc15.docking.org/substances/ZINC000003831490

PubMed

Title	Date	PubMed
		252160703
Efficacy of 101 antimicrobials and other agents on the development of Cryptosporidium parvum in vitro.	1996 Dec	9039272

Patents

Sample Use Guides

In Vivo Use Guide

Initial Therapy : Adults: 3 to 4 g daily in evenly divided doses with dosage intervals not exceeding eight hours. In some cases, it is advisable to initiate therapy with a smaller dosage, e.g., 1 to 2 g daily, to reduce possible gastrointestinal intolerance. If daily doses exceeding 4 g are required to achieve desired effects, the increased risk of toxicity should be kept in mind. Children, six years of age and older: 40 to 60 mg/kg body weight in each 24-hour period, divided into 3 to 6 doses. Maintenance Therapy : Adults: 2 g daily. Children, six years of age and older: 30 mg/kg body weight in each 24-hour period, divided into 4 doses.

Route of Administration: Oral

In Vitro Use Guide

Inhibition of arachidonate 5-lipoxygenase by sulfasalazine and its major metabolites was observed at higher concentrations (2-3 mM).

Name

Type

Language

Azulfidine

Preferred Name

English

Sulfasalazine

Official Name

English

Sulfasalazine [USAN]

Common Name

English

Sulfasalazine [INN]

Common Name

English

Sulfasalazine [ORANGE BOOK]

Common Name

English

Salazosulfapyridine [JAN]

Common Name

English

Salazopyrin

Brand Name

English

Sulfasalazine [EP MONOGRAPH]

Common Name

English

Sulfasalazine [MART.]

Common Name

English

Sulfasalazine [MI]

Common Name

English

Sulfasalazine [USP-RS]

Common Name

English

Sulfasalazine [VANDF]

Common Name

English

Sulfasalazinum [WHO-IP LATIN]

Common Name

English

Salicylazosulfapyridine

Common Name

English

NSC-203730

Code

English

NSC-667219

Code

English

Sulfasalazine [WHO-DD]

Common Name

English

Sulfasalazine [USP MONOGRAPH]

Common Name

English

Benzosulfa

Common Name

English

Sulfasalazine [IARC]

Common Name

English

SULFASALAZOPYRIDINE

Common Name

English

Sulfasalazine [WHO-IP]

Common Name

English

2-Hydroxy-5-((4-((2-pyridinylamino)sulfonyl)phenyl)azo)benzoic acid [WHO-IP]

Systematic Name

English

Benzoic acid, 2-hydroxy-5-[2-[4-[(2-pyridinylamino)sulfonyl]phenyl]diazenyl]-

Systematic Name

English

Sulfasalazine [HSDB]

Common Name

English

Sulphasalazine

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000005760