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Identification
Name Mesalazine
Accession Number DB00244 (APRD01098)
Type small molecule
Groups approved
Description

An anti-inflammatory agent, structurally related to the salicylates, which is active in inflammatory bowel disease. It is considered to be the active moiety of sulphasalazine. (From Martindale, The Extra Pharmacopoeia, 30th ed)
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • 5-aminosalicylate
  • 5-aminosalicylic acid
  • 5-ASA
  • Mesalamine
Brand names
  • Asacol
  • Asacolitin
  • Canasa
  • Claversal
  • Fisalamine
  • Lixacol
  • Mesasal
  • Pentasa
  • Rowasa
  • Salofalk
Brand name mixtures Not Available
Categories Not Available
CAS number 89-57-6
Weight Average: 153.1354
Monoisotopic: 153.042593095
Chemical Formula C7H7NO3
InChI Key InChIKey=KBOPZPXVLCULAV-UHFFFAOYSA-N
InChI
InChI=1S/C7H7NO3/c8-4-1-2-6(9)5(3-4)7(10)11/h1-3,9H,8H2,(H,10,11)
Plain Text
IUPAC Name
5-amino-2-hydroxybenzoic acid
SMILES
NC1=CC=C(O)C(=C1)C(O)=O
Plain Text
Mass Spec show (8.5 KB)
Taxonomy
Kingdom Organic
Classes
  • Salicylates and Derivatives
  • Aminobenzoates
  • Aminophenols and Derivatives
Substructures
  • Hydroxy Compounds
  • Benzyl Alcohols and Derivatives
  • Acetates
  • Benzoates
  • Salicylates and Derivatives
  • Phenols and Derivatives
  • Aliphatic and Aryl Amines
  • Benzene and Derivatives
  • Aminobenzoates
  • Aminophenols and Derivatives
  • Carboxylic Acids and Derivatives
  • Aromatic compounds
  • Benzoyl Derivatives
  • Phenyl Esters
  • Anilines
Pharmacology
Indication For the treatment of active ulcerative proctitis.
Pharmacodynamics Mesalazine (INN, BAN), also known as Mesalamine (USAN) or 5-aminosalicylic acid (5-ASA), is an anti-inflammatory drug used to treat inflammation of the digestive tract (Crohn's disease) and mild to moderate ulcerative colitis. Mesalazine is a bowel-specific aminosalicylate drug that is metabolized in the gut and has its predominant actions there, thereby having fewer systemic side effects. As a derivative of salicylic acid, 5-ASA is also an antioxidant that traps free radicals, which are potentially damaging by-products of metabolism.
Mechanism of action Although the mechanism of action of mesalazine is not fully understood, it appears to be topical rather than systemic. Mucosal production of arachidonic acid metabolites, both through the cyclooxygenase pathways, i.e., prostanoids, and through the lipoxygenase pathways, i.e., leukotrienes and hydroxyeicosatetraenoic acids, is increased in patients with chronic inflammatory bowel disease, and it is possible that mesalazine diminishes inflammation by blocking cyclooxygenase and inhibiting prostaglandin production in the colon.
Absorption 20 to 30% absorbed following oral administration. 10 to 35% absorbed from the colon (rectal suppository) - extent of absorption is determined by the length of time the drug is retained in the colon.
Volume of distribution Not Available
Protein binding About 80% of N-Ac-5-ASA is bound to plasma proteins, whereas 40% of mesalamine is protein bound.
Metabolism

Rapidly and extensively metabolized, mainly to N-acetyl-5-ASA (Ac-5-ASA) in the intestinal mucosal wall and the liver. Ac-5-ASA is further acetylated (deactivated) in at least 2 sites, the colonic epithelium and the liver.
Route of elimination Approximately 28% of the mesalamine in Asacol tablets is absorbed after oral ingestion, leaving the remainder available for topical action and excretion in the feces. It is excreted mainly by the kidney as N-acetyl-5-aminosalicylic acid.
Half life The mean elimination half-life was 5 hours for 5-ASA and six hours for N-acetyl-5-ASA following the initial dose. At steady state, the mean elimination half-life was seven hours for both 5-ASA and N-acetyl-5-ASA.
Clearance Not Available
Toxicity Oral, mouse: LD50 = 3370 mg/kg; Oral, rat: LD50 = 2800 mg/kg; Skin, rabbit: LD50 = >5 gm/kg. There have been no documented reports of serious toxicity in man resulting from massive overdosing with mesalamine. Under ordinary circumstances, mesalazine absorption from the colon is limited.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Salix pharmaceuticals inc
  • Shire development inc
  • Perrigo israel pharmaceuticals ltd
  • Teva pharmaceuticals usa inc
  • Alaven pharmaceutical llc
  • Axcan pharma us inc
  • Warner chilcott pharmaceuticals inc
Packagers
Dosage forms
Form Route Strength
Enema Rectal
Suppository Rectal
Suspension Rectal
Tablet, coated Oral
Tablet, delayed release Oral
Tablet, extended release Oral
Prices
Unit description Cost Unit
Canasa 30 1000 mg Suppository Box 488.32 USD box
Canasa 1000 mg suppository 13.88 USD suppository
Salofalk (4 g/60 g) 4 g/enm Enema 6.73 USD enema
Canasa 500 mg suppository 6.24 USD suppository
Pentasa (4 g/100 Ml) 4 g/enm Enema 5.02 USD enema
Pentasa (1 g/100Ml) 1 g/enm Enema 4.17 USD enema
Salofalk (2 g/60 g) 2 g/enm Enema 3.96 USD enema
Asacol hd dr 800 mg tablet 3.88 USD tablet
Pentasa 500 mg capsule 2.66 USD capsule
Asacol 400 mg Enteric Coated Tabs 2.22 USD tab
Asacol ec 400 mg tablet 1.94 USD tablet
Salofalk 1000 mg Suppository 1.81 USD suppository
Pentasa 1 g Suppository 1.8 USD suppository
Salofalk 500 mg Suppository 1.23 USD suppository
Asacol 800 800 mg Enteric-Coated Tablet 1.14 USD tablet
Pentasa 250 mg capsule 1.07 USD capsule
Mesasal 500 mg Enteric-Coated Tablet 0.69 USD tablet
Pentasa 500 mg Sustained-Release Tablet 0.63 USD tablet
Asacol 400 mg Enteric-Coated Tablet 0.59 USD tablet
Salofalk 500 mg Enteric-Coated Tablet 0.56 USD tablet
Novo-5 Asa 400 mg Enteric-Coated Tablet 0.42 USD tablet
Rowasa 4 gm/60 ml enema 0.41 USD ml
Patents
Country Patent Number Approved Expires
United States 7645801 2007-07-24 2027-07-24
United States 5541170 1993-07-30 2013-07-30
Canada 2444814 2009-06-09 2021-10-24
Canada 2111697 2002-08-20 2012-06-16
Properties
State solid
Melting point 283 oC
Experimental Properties
Property Value Source
water solubility 0.84 g/L at 20°C PhysProp
logP 1.2 PhysProp
Predicted Properties
Property Value Source
water solubility 1.22e+01 g/l ALOGPS
logP 0.75 ALOGPS
logP -0.49 ChemAxon Molconvert
logS -1.10 ALOGPS
pKa 15.48 ChemAxon Molconvert
hydrogen acceptor count 4 ChemAxon Molconvert
hydrogen donor count 3 ChemAxon Molconvert
polar surface area 83.55 ChemAxon Molconvert
rotatable bond count 1 ChemAxon Molconvert
refractivity 40.00 ChemAxon Molconvert
polarizability 14.26 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Link
External Links
Resource Link
KEGG Drug D00377 Link_out
PubChem Compound 4075 Link_out
PubChem Substance 46509142 Link_out
ChemSpider 3933 Link_out
ChEBI 6775 Link_out
ChEMBL 6775 Link_out
Therapeutic Targets Database DAP000729 Link_out
PharmGKB PA450384 Link_out
Drug Product Database 0 Link_out
RxList http://www.rxlist.com/cgi/generic2/canasa.htm Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/row1389.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Mesalazine Link_out
ATC Codes
  • A07EC02
AHFS Codes
  • 56:36.00
PDB Entries Not Available
FDA label Not Available
MSDS show (67.7 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Take without regard to meals.
Targets

1. Prostaglandin G/H synthase 2

Pharmacological action: yes
Actions: inhibitor

May have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity

Organism class: human
UniProt ID: P35354 Link_out
Gene: PTGS2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

2. Prostaglandin G/H synthase 1

Pharmacological action: yes
Actions: inhibitor

May play an important role in regulating or promoting cell proliferation in some normal and neoplastically transformed cells

Organism class: human
UniProt ID: P23219 Link_out
Gene: PTGS1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

3. Arachidonate 5-lipoxygenase

Pharmacological action: yes
Actions: inhibitor
Organism class: human
UniProt ID: P09917 Link_out
Gene: ALOX5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

4. Peroxisome proliferator-activated receptor gamma

Pharmacological action: yes
Actions: agonist

Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the receptor binds to a promoter element in the gene for acyl-CoA oxidase and activates its transcription. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis

Organism class: human
UniProt ID: P37231 Link_out
Gene: PPARG Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown
Actions: inhibitor
UniProt ID: O15111 Link_out
Gene: CHUK
SNPs: SNPJam Report Link_out

References:
  1. Bantel H, Berg C, Vieth M, Stolte M, Kruis W, Schulze-Osthoff K: Mesalazine inhibits activation of transcription factor NF-kappaB in inflamed mucosa of patients with ulcerative colitis. Am J Gastroenterol. 2000 Dec;95(12):3452-7. 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
  3. 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

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

Pharmacological action: unknown
Actions: inhibitor

Phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. Also phosphorylates NCOA3

Organism class: human
UniProt ID: O14920 Link_out
Gene: IKBKB Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Bantel H, Berg C, Vieth M, Stolte M, Kruis W, Schulze-Osthoff K: Mesalazine inhibits activation of transcription factor NF-kappaB in inflamed mucosa of patients with ulcerative colitis. Am J Gastroenterol. 2000 Dec;95(12):3452-7. 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
  3. 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
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:02

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.