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Identification
NameSulfasalazine
Accession NumberDB00795  (APRD00152, DB08518)
Typesmall molecule
Groupsapproved
Description

A drug that is used in the management of inflammatory bowel diseases. Its activity is generally considered to lie in its metabolic breakdown product, 5-aminosalicylic acid (see mesalamine) released in the colon. (From Martindale, The Extra Pharmacopoeia, 30th ed, p907)

Structure
Thumb
Synonyms
SynonymLanguageCode
AzopyrinNot AvailableIS
SalazosulfapyridineNot AvailableJAN
SulfasalazinGermanINN
Sulfasalazina SpanishINN
SulfasalazineFrenchINN
SulfasalazinumLatinINN
SaltsNot Available
Brand names
NameCompany
AsasurfanChoseido Pharmaceutical
AzulfdidinaPfizer
AzulfidinePfizer
AzulfinApsen
BomeconFu Seng
Colo-PleonSanofi-Aventis
DisalazinAC Farma
EminapyrinTaiyo Pharmaceutical
FlogostopIvax
IwataCadila
LanofenTaisho Yakuhin
LazafinNovell
PleonSanofi-Aventis
Pyralin ENPfizer
ReumazinAristopharma
SaazIpca
Saaz-DSIpca
SalasopyrineUpjohn
SalazarCadila
SalazidinHelcor
SalazineOpsonin
SalazopirinaJaba Recordati
SalazoprinCazi
SalazopyrinPfizer
Salazopyrin ENPfizer
Salazopyrin EN-TabsPharmacia
SulcolonBernofarm
SulfacolDrug International
WeiliufenSunve
ZopyrinHan Lim
Brand mixturesNot Available
Categories
CAS number599-79-1
WeightAverage: 398.393
Monoisotopic: 398.068490268
Chemical FormulaC18H14N4O5S
InChI KeyNCEXYHBECQHGNR-QZQOTICOSA-N
InChI
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+
IUPAC Name
2-hydroxy-5-[(E)-2-{4-[(pyridin-2-yl)sulfamoyl]phenyl}diazen-1-yl]benzoic acid
SMILES
OC(=O)C1=CC(=CC=C1O)\N=N\C1=CC=C(C=C1)S(=O)(=O)NC1=NC=CC=C1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassBenzenesulfonamides
Direct parentAminobenzenesulfonamides
Alternative parentsAminobenzoic Acid Derivatives; Salicylic Acids; Benzoic Acids; Aminophenols; Benzoyl Derivatives; Aminopyridines and Derivatives; Sulfonyls; Sulfonamides; Azo Compounds; Enolates; Polyamines; Enols; Carboxylic Acids
Substituentsbenzoic acid; benzoic acid or derivative; benzoyl; aminophenol; aminopyridine; phenol derivative; pyridine; sulfonyl; sulfonamide; sulfonic acid derivative; azo compound; enol; carboxylic acid derivative; enolate; carboxylic acid; polyamine; amine; organonitrogen compound
Classification descriptionThis compound belongs to the aminobenzenesulfonamides. These are organic compounds containing a benzenesulfonamide moiety with an amine group attached to the benzene ring.
Pharmacology
IndicationFor the treatment of Crohn's disease and rheumatoid arthritis as a second-line agent.
PharmacodynamicsSulfasalazine is an anti-inflammatory indicated for the treatment of ulcerative colitis and rheumatoid arthritis.
Mechanism of actionThe 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 vitro models, 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.
AbsorptionNot Available
Volume of distribution
  • 7.5 ± 1.6 L
Protein bindingNot Available
Metabolism
Route of eliminationThe majority of 5-ASA stays within the colonic lumen and is excreted as 5-ASA and acetyl-5-ASA with the feces.
Half life5-10 hours
Clearance
  • 1 L/h [IV administration]
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9156
Blood Brain Barrier - 0.7294
Caco-2 permeable - 0.6893
P-glycoprotein substrate Non-substrate 0.8405
P-glycoprotein inhibitor I Non-inhibitor 0.9096
P-glycoprotein inhibitor II Non-inhibitor 0.853
Renal organic cation transporter Non-inhibitor 0.8956
CYP450 2C9 substrate Non-substrate 0.6445
CYP450 2D6 substrate Non-substrate 0.9116
CYP450 3A4 substrate Non-substrate 0.7557
CYP450 1A2 substrate Non-inhibitor 0.9046
CYP450 2C9 substrate Inhibitor 0.8948
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Non-inhibitor 0.923
CYP450 3A4 substrate Non-inhibitor 0.8309
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8895
Ames test Non AMES toxic 0.9133
Carcinogenicity Non-carcinogens 0.6468
Biodegradation Not ready biodegradable 0.9472
Rat acute toxicity 1.4383 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.939
hERG inhibition (predictor II) Non-inhibitor 0.821
Pharmacoeconomics
Manufacturers
  • Pharmacia and upjohn co
  • Vintage pharmaceuticals inc
  • Watson laboratories inc
  • Solvay pharmaceuticals
  • Heritage pharmaceuticals inc
  • Mutual pharmaceutical co inc
  • Sandoz inc
  • Superpharm corp
Packagers
Dosage forms
FormRouteStrength
TabletOral
Tablet, coatedOral
Prices
Unit descriptionCostUnit
Sulfasalazine powder2.14USDg
Azulfidine EN-tabs 500 mg Enteric Coated Tabs0.73USDtab
Azulfidine entab 500 mg0.69USDtablet
Azulfidine 500 mg tablet0.59USDtablet
Salazopyrin En-Tabs 500 mg Enteric-Coated Tablet0.45USDtablet
Sulfasalazine 500 mg Enteric Coated Tabs0.4USDtab
Pms-Sulfasalazine 500 mg Enteric-Coated Tablet0.34USDtablet
Salazopyrin 500 mg Tablet0.28USDtablet
Sulfasalazine 500 mg tablet0.25USDtablet
Sulfazine 500 mg tablet0.25USDtablet
Pms-Sulfasalazine 500 mg Tablet0.22USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point220 dec °CPhysProp
logP2.5Not Available
Caco2 permeability-6.33ADME Research, USCD
Predicted Properties
PropertyValueSource
water solubility4.64e-02 g/lALOGPS
logP2.92ALOGPS
logP3.94ChemAxon
logS-3.9ALOGPS
pKa (strongest acidic)3.3ChemAxon
pKa (strongest basic)2.4ChemAxon
physiological charge-2ChemAxon
hydrogen acceptor count8ChemAxon
hydrogen donor count3ChemAxon
polar surface area141.31ChemAxon
rotatable bond count5ChemAxon
refractivity104.6ChemAxon
polarizability39.69ChemAxon
number of rings3ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD00448
KEGG CompoundC07316
PubChem Compound5359476
PubChem Substance46505451
ChemSpider4510284
ChEBI9334
ChEMBLCHEMBL421
Therapeutic Targets DatabaseDAP000153
PharmGKBPA451547
HETSAS
Drug Product Database685933
RxListhttp://www.rxlist.com/cgi/generic/sulfasal.htm
Drugs.comhttp://www.drugs.com/cdi/sulfasalazine.html
WikipediaSulfasalazine
ATC CodesA07EC01
AHFS Codes
  • 08:12.20
PDB EntriesNot Available
FDA labelshow(796 KB)
MSDSshow(72.8 KB)
Interactions
Drug Interactions
Drug
AzathioprineSulfasalazine may increase the toxicity of thiopurine, azathioprine.
Azilsartan medoxomilIncreases toxicity of each. May deteriorate renal function, particularly in volume depleted or elderly patients. Decreases effects of azilsartan by antagonism.
ChlorpropamideSulfonamide/sulfonylurea: possible hypoglycemia
CyclosporineThe sulfonamide decreases the effect of cyclosporine
DigoxinSulfasalazine may decrease the effect of digoxin.
MercaptopurineSulfasalazine may increase the toxicity of thiopurine, mercaptopurine.
TioguanineSulfasalazine may increase the toxicity of thiopurine, thioguanine.
Food Interactions
  • May take Vitamin D.
  • Take with a full glass of water No iron, zinc or fluoride within 2 hours of taking this medication.
  • Take with food.

Targets

1. Arachidonate 5-lipoxygenase

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Arachidonate 5-lipoxygenase P09917 Details

References:

  1. Nielsen OH, Bukhave K, Elmgreen J, Ahnfelt-Ronne I: Inhibition of 5-lipoxygenase pathway of arachidonic acid metabolism in human neutrophils by sulfasalazine and 5-aminosalicylic acid. Dig Dis Sci. 1987 Jun;32(6):577-82. Pubmed
  2. Allgayer H, Eisenburg J, Paumgartner G: Soybean lipoxygenase inhibition: studies with the sulphasalazine metabolites N-acetylaminosalicylic acid, 5-aminosalicylic acid and sulphapyridine. Eur J Clin Pharmacol. 1984;26(4):449-51. Pubmed
  3. Sircar JC, Schwender CF, Carethers ME: Inhibition of soybean lipoxygenase by sulfasalazine and 5-aminosalicylic acid: a possible mode of action in ulcerative colitis. Biochem Pharmacol. 1983 Jan 1;32(1):170-2. Pubmed

2. Prostaglandin G/H synthase 2

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Prostaglandin G/H synthase 2 P35354 Details

References:

  1. Mifflin RC, Saada JI, Di Mari JF, Valentich JD, Adegboyega PA, Powell DW: Aspirin-mediated COX-2 transcript stabilization via sustained p38 activation in human intestinal myofibroblasts. Mol Pharmacol. 2004 Feb;65(2):470-8. Pubmed
  2. Generini S, Fiori G, Matucci Cerinic M: Therapy of spondylarthropathy in inflammatory bowel disease. Clin Exp Rheumatol. 2002 Nov-Dec;20(6 Suppl 28):S88-94. Pubmed
  3. Distrutti E, Sediari L, Mencarelli A, Renga B, Orlandi S, Russo G, Caliendo G, Santagada V, Cirino G, Wallace JL, Fiorucci S: 5-Amino-2-hydroxybenzoic acid 4-(5-thioxo-5H-[1,2]dithiol-3yl)-phenyl ester (ATB-429), a hydrogen sulfide-releasing derivative of mesalamine, exerts antinociceptive effects in a model of postinflammatory hypersensitivity. J Pharmacol Exp Ther. 2006 Oct;319(1):447-58. Epub 2006 Jul 19. Pubmed
  4. Cipolla G, Crema F, Sacco S, Moro E, de Ponti F, Frigo G: Nonsteroidal anti-inflammatory drugs and inflammatory bowel disease: current perspectives. Pharmacol Res. 2002 Jul;46(1):1-6. Pubmed
  5. Pruzanski W, Stefanski E, Vadas P, Ramamurthy NS: Inhibition of extracellular release of proinflammatory secretory phospholipase A2 (sPLA2) by sulfasalazine: a novel mechanism of anti-inflammatory activity. Biochem Pharmacol. 1997 Jun 15;53(12):1901-7. Pubmed

3. Prostaglandin G/H synthase 1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Prostaglandin G/H synthase 1 P23219 Details

References:

  1. Allgayer H: Review article: mechanisms of action of mesalazine in preventing colorectal carcinoma in inflammatory bowel disease. Aliment Pharmacol Ther. 2003 Sep;18 Suppl 2:10-4. Pubmed

4. Peroxisome proliferator-activated receptor gamma

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Peroxisome proliferator-activated receptor gamma P37231 Details

References:

  1. Rousseaux C, Lefebvre B, Dubuquoy L, Lefebvre P, Romano O, Auwerx J, Metzger D, Wahli W, Desvergne B, Naccari GC, Chavatte P, Farce A, Bulois P, Cortot A, Colombel JF, Desreumaux P: Intestinal antiinflammatory effect of 5-aminosalicylic acid is dependent on peroxisome proliferator-activated receptor-gamma. J Exp Med. 2005 Apr 18;201(8):1205-15. Epub 2005 Apr 11. Pubmed
  2. Schwab M, Reynders V, Loitsch S, Shastri YM, Steinhilber D, Schroder O, Stein J: PPARgamma is involved in mesalazine-mediated induction of apoptosis and inhibition of cell growth in colon cancer cells. Carcinogenesis. 2008 Jul;29(7):1407-14. Epub 2008 Jun 9. Pubmed
  3. Linard C, Gremy O, Benderitter M: Reduction of peroxisome proliferation-activated receptor gamma expression by gamma-irradiation as a mechanism contributing to inflammatory response in rat colon: modulation by the 5-aminosalicylic acid agonist. J Pharmacol Exp Ther. 2008 Mar;324(3):911-20. Epub 2007 Dec 12. Pubmed
  4. Desreumaux P, Ghosh S: Review article: mode of action and delivery of 5-aminosalicylic acid – new evidence. Aliment Pharmacol Ther. 2006 Sep;24 Suppl 1:2-9. Pubmed

5. Inhibitor of nuclear factor kappa-B kinase subunit alpha

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Inhibitor of nuclear factor kappa-B kinase subunit alpha O15111 Details

References:

  1. Weber CK, Liptay S, Wirth T, Adler G, Schmid RM: Suppression of NF-kappaB activity by sulfasalazine is mediated by direct inhibition of IkappaB kinases alpha and beta. Gastroenterology. 2000 Nov;119(5):1209-18. Pubmed
  2. Allgayer H: Review article: mechanisms of action of mesalazine in preventing colorectal carcinoma in inflammatory bowel disease. Aliment Pharmacol Ther. 2003 Sep;18 Suppl 2:10-4. Pubmed

6. Inhibitor of nuclear factor kappa-B kinase subunit beta

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Inhibitor of nuclear factor kappa-B kinase subunit beta O14920 Details

References:

  1. Weber CK, Liptay S, Wirth T, Adler G, Schmid RM: Suppression of NF-kappaB activity by sulfasalazine is mediated by direct inhibition of IkappaB kinases alpha and beta. Gastroenterology. 2000 Nov;119(5):1209-18. Pubmed
  2. Allgayer H: Review article: mechanisms of action of mesalazine in preventing colorectal carcinoma in inflammatory bowel disease. Aliment Pharmacol Ther. 2003 Sep;18 Suppl 2:10-4. Pubmed

7. Cystine/glutamate transporter

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cystine/glutamate transporter Q9UPY5 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Gout PW, Buckley AR, Simms CR, Bruchovsky N: Sulfasalazine, a potent suppressor of lymphoma growth by inhibition of the x©- cystine transporter: a new action for an old drug. Leukemia. 2001 Oct;15(10):1633-40. Pubmed

8. Acetyl-CoA acetyltransferase, mitochondrial

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Acetyl-CoA acetyltransferase, mitochondrial P24752 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Faison LD, White HL: Sulfasalazine inhibits lyso-PAF: acetyl-COA acetyltransferase. Prostaglandins. 1992 Sep;44(3):245-9. Pubmed

9. Thromboxane-A synthase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Thromboxane-A synthase P24557 Details

References:

  1. Stenson WF, Lobos E: Inhibition of platelet thromboxane synthetase by sulfasalazine. Biochem Pharmacol. 1983 Jul 15;32(14):2205-9. Pubmed

10. Phospholipase A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Phospholipase A2 P04054 Details

References:

  1. Pruzanski W, Stefanski E, Vadas P, Ramamurthy NS: Inhibition of extracellular release of proinflammatory secretory phospholipase A2 (sPLA2) by sulfasalazine: a novel mechanism of anti-inflammatory activity. Biochem Pharmacol. 1997 Jun 15;53(12):1901-7. Pubmed

Enzymes

1. Cytochrome P450 3A5

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A5 P20815 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

Transporters

1. ATP-binding cassette sub-family G member 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
ATP-binding cassette sub-family G member 2 Q9UNQ0 Details

References:

  1. Karlsson JE, Heddle C, Rozkov A, Rotticci-Mulder J, Tuvesson O, Hilgendorf C, Andersson TB: High-activity p-glycoprotein, multidrug resistance protein 2, and breast cancer resistance protein membrane vesicles prepared from transiently transfected human embryonic kidney 293-epstein-barr virus nuclear antigen cells. Drug Metab Dispos. 2010 Apr;38(4):705-14. Epub 2010 Jan 13. Pubmed
  2. Shukla S, Zaher H, Hartz A, Bauer B, Ware JA, Ambudkar SV: Curcumin inhibits the activity of ABCG2/BCRP1, a multidrug resistance-linked ABC drug transporter in mice. Pharm Res. 2009 Feb;26(2):480-7. Epub 2008 Oct 9. Pubmed
  3. Dahan A, Amidon GL: Small intestinal efflux mediated by MRP2 and BCRP shifts sulfasalazine intestinal permeability from high to low, enabling its colonic targeting. Am J Physiol Gastrointest Liver Physiol. 2009 Aug;297(2):G371-7. Epub 2009 Jun 18. Pubmed

2. Canalicular multispecific organic anion transporter 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Canalicular multispecific organic anion transporter 1 Q92887 Details

References:

  1. Dahan A, Amidon GL: Small intestinal efflux mediated by MRP2 and BCRP shifts sulfasalazine intestinal permeability from high to low, enabling its colonic targeting. Am J Physiol Gastrointest Liver Physiol. 2009 Aug;297(2):G371-7. Epub 2009 Jun 18. Pubmed

3. Proton-coupled folate transporter

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Proton-coupled folate transporter Q96NT5 Details

References:

  1. Nakai Y, Inoue K, Abe N, Hatakeyama M, Ohta KY, Otagiri M, Hayashi Y, Yuasa H: Functional characterization of human proton-coupled folate transporter/heme carrier protein 1 heterologously expressed in mammalian cells as a folate transporter. J Pharmacol Exp Ther. 2007 Aug;322(2):469-76. Epub 2007 May 2. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:12