Balsalazide (T3D2957)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (4)XML
Targets (4)
Record Information
Version2.0
Creation Date2009-07-21 20:28:10 UTC
Update Date2014-12-24 20:25:54 UTC
Accession NumberT3D2957
Identification
Common NameBalsalazide
ClassSmall Molecule
DescriptionBalsalazide is an anti-inflammatory drug used in the treatment of Inflammatory Bowel Disease. It is sold under the name "Colazal" in the US and "Colazide" in the UK. The chemical name is (E)-5-[[-4-(2-carboxyethyl) aminocarbonyl] phenyl]azo] -2-hydroxybenzoic acid. It is usually administered as the disodium salt. Balsalazide releases mesalazine, also known as 5-aminosalicylic acid, or 5-ASA, in the large intestine. Its advantage over that drug in the treatment of Ulcerative colitis is believed to be the delivery of the active agent past the small intestine to the large intestine, the active site of ulcerative colitis.
Compound Type
  • Amide
  • Amine
  • Anti-Inflammatory Agent, Non-Steroidal
  • Anti-Ulcer Agent
  • Drug
  • Ester
  • Gastrointestinal Agent
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
(e)-5-((4-(((2-Carboxyethyl)amino)carbonyl)phenyl)azo)-2-hydroxybenzoic acid
(e)-5-({p-[(2-carboxyethyl)carbamoyl]phenyl}azo)-2-salicylic acid
3-(2-{4-[(2-carboxyethyl)carbamoyl]phenyl}hydrazinylidene)-6-oxocyclohexa-1,4-diene-1-carboxylic acid
5-[4-(2-Carboxy-ethylcarbamoyl)-phenylazo]-2-hydroxy-benzoic acid
Balsalazida
Balsalazide disodium
Balsalazido
Balsalazidum
Colazal
Colazide
GIAZO
Chemical FormulaC17H15N3O6
Average Molecular Mass357.318 g/mol
Monoisotopic Mass357.096 g/mol
CAS Registry Number80573-04-2
IUPAC Name5-[(E)-2-{4-[(2-carboxyethyl)carbamoyl]phenyl}diazen-1-yl]-2-hydroxybenzoic acid
Traditional Namebalsalazide
SMILESOC(=O)CCNC(=O)C1=CC=C(C=C1)\N=N\C1=CC(C(O)=O)=C(O)C=C1
InChI IdentifierInChI=1S/C17H15N3O6/c21-14-6-5-12(9-13(14)17(25)26)20-19-11-3-1-10(2-4-11)16(24)18-8-7-15(22)23/h1-6,9,21H,7-8H2,(H,18,24)(H,22,23)(H,25,26)/b20-19+
InChI KeyInChIKey=IPOKCKJONYRRHP-FMQUCBEESA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as azobenzenes. These are organonitrogen aromatic compounds that contain a central azo group, where each nitrogen atom is conjugated to a benzene ring.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassAzobenzenes
Sub ClassNot Available
Direct ParentAzobenzenes
Alternative Parents
Substituents
  • Azobenzene
  • Beta amino acid or derivatives
  • Hydroxybenzoic acid
  • Salicylic acid or derivatives
  • Salicylic acid
  • Benzoic acid
  • Benzoic acid or derivatives
  • Benzamide
  • Benzoyl
  • 1-hydroxy-2-unsubstituted benzenoid
  • Phenol
  • Benzenoid
  • Dicarboxylic acid or derivatives
  • Monocyclic benzene moiety
  • Vinylogous acid
  • Azo compound
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Carboxylic acid derivative
  • Carboxylic acid
  • Carbonyl group
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organooxygen compound
  • Organic oxygen compound
  • Organopnictogen compound
  • Organonitrogen compound
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityFreely soluble as disodium salt
LogP1.3
Predicted Properties
PropertyValueSource
Water Solubility0.062 g/LALOGPS
logP3.37ALOGPS
logP3.17ChemAxon
logS-3.8ALOGPS
pKa (Strongest Acidic)3.06ChemAxon
pKa (Strongest Basic)-0.033ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area148.65 ŲChemAxon
Rotatable Bond Count7ChemAxon
Refractivity94.37 m³·mol⁻¹ChemAxon
Polarizability35.98 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0ldi-1393000000-af92622c6ce32e802a992017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (3 TMS) - 70eV, Positivesplash10-052f-2239460000-dd6d65f067d80197bd6e2017-10-06View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-05mo-1359000000-5ac19318b9222056db992016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-01b9-4194000000-a389ca20ea5f71b14f1b2016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00or-9460000000-058a3d277554ae6ad3a02016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0r00-0859000000-0815df00a696a3bf2ef92016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0cdl-1596000000-f30b936242fc2a51a3bc2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4i-1920000000-ab19fc8210a3b9bf159a2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014i-0090000000-938e67d0a29d75e915602021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0297-0094000000-71c0a9165a9dbb26d8ed2021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0fvi-0590000000-6f84da2d9032ab43467d2021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-0019000000-5cde35cdf9191a2d07212021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-001l-0092000000-e9ef5ce26a4f3979c2122021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-2290000000-1ff988f1dc562e4db92f2021-10-11View Spectrum
Toxicity Profile
Route of ExposureOral. Low and variable, intact balsalazide is poorly absorbed systemically.
Mechanism of ToxicityThe mechanism of action of 5-aminosalicylic acid is unknown, but appears exert its anti-inflammatory effects locally (in the GI tract) rather than systemically. Mucosal production of arachidonic acid metabolites, both through the cyclooxygenase pathways (catalyzes the formation of prostaglandin precursors from arachidonic acid), and through the lipoxygenase pathways (catalyzes the formation of leukotrienes and hydroxyeicosatetraenoic acids from arachidonic acid and its metabolites), is increased in patients with chronic inflammatory bowel disease. Therefore, it is possible that 5-aminosalicylic acid diminishes inflammation by blocking production of arachidonic acid metabolites in the colon through both the inhibition of cyclooxygenase and lipoxygenase.
MetabolismCleaved in the colon via bacterial azoreduction to 5-aminosalicylic acid (5–ASA) and 4-aminobenzoyl-beta-alanine, the inactive carrier moiety. Route of Elimination: The products of the azoreduction of this compound, 5-ASA and 4-aminobenzoyl-beta-alanine, and their N-acetylated metabolites have been identified in plasma, urine and feces. Following single-dose administration of 2.25 g COLAZAL (three 750 mg capsules) under fasting conditions in healthy subjects, mean urinary recovery of balsalazide, 5-ASA, and N-Ac-5-ASA was 0.20%, 0.22% and 10.2%, respectively. Half Life: Half-life could not be determined.
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesUsed in the treatment of inflammatory bowel disease. [Wikipedia]
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsSymptoms include headache, abdominal pain, upset stomach, dry mouth, yellowing of the skin or eyes, bloating or swelling of the stomach, and fever, sore throat, or flu-like symptoms. (5)
TreatmentIf an overdose occurs with Balsalazide, treatment should be supportive, with particular attention to correction of electrolyte abnormalities. (4)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB01014
HMDB IDHMDB15149
PubChem Compound ID6335412
ChEMBL IDCHEMBL102265
ChemSpider ID10662422
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI ID267413
BioCyc IDNot Available
CTD IDNot Available
Stitch IDBalsalazide
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkBalsalazide
References
Synthesis Reference

Eckardt C. G. Wolf, Nageib Mohamed, Bhaskar Reddy Guntoori, “Safe process for the preparation of balsalazide.” U.S. Patent US07271253, issued September 18, 2007.

MSDST3D2957.pdf
General References
  1. Wiggins JB, Rajapakse R: Balsalazide: a novel 5-aminosalicylate prodrug for the treatment of active ulcerative colitis. Expert Opin Drug Metab Toxicol. 2009 Oct;5(10):1279-84. doi: 10.1517/17425250903206996. [19743890 ]
  2. Ragunath K, Williams JG: Review article: balsalazide therapy in ulcerative colitis. Aliment Pharmacol Ther. 2001 Oct;15(10):1549-54. [11563993 ]
  3. Drugs.com [Link]
  4. RxList: The Internet Drug Index (2009). [Link]
  5. Medline Plus. Balsalazide [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Peroxisome proliferator-activated receptor gamma
General Function:
Zinc ion binding
Specific Function:
Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE) and modulates the transcription of its target genes, such as acyl-CoA oxidase. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. ARF6 acts as a key regulator of the tissue-specific adipocyte P2 (aP2) enhancer. Acts as a critical regulator of gut homeostasis by suppressing NF-kappa-B-mediated proinflammatory responses. Plays a role in the regulation of cardiovascular circadian rhythms by regulating the transcription of ARNTL/BMAL1 in the blood vessels (By similarity).
Gene Name:
PPARG
Uniprot ID:
P37231
Molecular Weight:
57619.58 Da
References
  1. Tursi A: Balsalazide in treating colonic diseases. Expert Opin Drug Metab Toxicol. 2009 Dec;5(12):1555-63. doi: 10.1517/17425250903228842. [19708827 ]
  2. Iacucci M, de Silva S, Ghosh S: Mesalazine in inflammatory bowel disease: a trendy topic once again? Can J Gastroenterol. 2010 Feb;24(2):127-33. [20151072 ]
  3. 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. [16939423 ]
  4. 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. [18077625 ]
Target Details
2. Arachidonate 5-lipoxygenase
General Function:
Iron ion binding
Specific Function:
Catalyzes the first step in leukotriene biosynthesis, and thereby plays a role in inflammatory processes.
Gene Name:
ALOX5
Uniprot ID:
P09917
Molecular Weight:
77982.595 Da
References
  1. Wiggins JB, Rajapakse R: Balsalazide: a novel 5-aminosalicylate prodrug for the treatment of active ulcerative colitis. Expert Opin Drug Metab Toxicol. 2009 Oct;5(10):1279-84. doi: 10.1517/17425250903206996. [19743890 ]
  2. Rask-Madsen J, Bukhave K, Laursen LS, Lauritsen K: 5-Lipoxygenase inhibitors for the treatment of inflammatory bowel disease. Agents Actions. 1992;Spec No:C37-46. [1359745 ]
Target Details
3. Prostaglandin G/H synthase 1
General Function:
Prostaglandin-endoperoxide synthase activity
Specific Function:
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gastric epithelial cells, it is a key step in the generation of prostaglandins, such as prostaglandin E2 (PGE2), which plays an important role in cytoprotection. In platelets, it is involved in the generation of thromboxane A2 (TXA2), which promotes platelet activation and aggregation, vasoconstriction and proliferation of vascular smooth muscle cells.
Gene Name:
PTGS1
Uniprot ID:
P23219
Molecular Weight:
68685.82 Da
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. [17139284 ]
  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. [17016423 ]
Target Details
4. Prostaglandin G/H synthase 2
General Function:
Prostaglandin-endoperoxide synthase activity
Specific Function:
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and brain, and in pathological conditions, such as in cancer. PTGS2 is responsible for production of inflammatory prostaglandins. Up-regulation of PTGS2 is also associated with increased cell adhesion, phenotypic changes, resistance to apoptosis and tumor angiogenesis. In cancer cells, PTGS2 is a key step in the production of prostaglandin E2 (PGE2), which plays important roles in modulating motility, proliferation and resistance to apoptosis.
Gene Name:
PTGS2
Uniprot ID:
P35354
Molecular Weight:
68995.625 Da
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. [17139284 ]
  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. [17016423 ]