Mesalazine

Overview

Description
A medication used to control Ulcerative Colitis, a disease that causes sores and inflammation in the digestive system.
Description
A medication used to control Ulcerative Colitis, a disease that causes sores and inflammation in the digestive system.
DrugBank ID
DB00244
Type
Small Molecule
US Approved
YES
Other Approved
YES
Clinical Trials
Phase 0
1
Phase 1
39
Phase 2
43
Phase 3
94
Phase 4
26
Therapeutic Categories
  • Aminosalicylate
  • Anti-Inflammatory Agents

Identification

Summary

Mesalazine is an aminosalicylate drug used to treat mild to moderate active ulcerative colitis and also to maintain remission once achieved.

Brand Names
Apriso, Asacol, Canasa, Delzicol, Lialda, Mezavant, Pentasa, Rowasa, Salofalk, Zaldyon
Generic Name
Mesalazine
DrugBank Accession Number
DB00244
Background

An anti-inflammatory agent, structurally related to the salicylates and non-steroidal anti-inflammatory drugs like acetylsalicylic acid, which is active in inflammatory bowel disease 2. Although demonstrably effective in treating and maintaining remission for ulcerative colitis, mesalazine has historically faced a number of issues regarding its lack of stability as a pharmaceutical agent 1. Throughout the late seventies and the eighties, important research initiatives developed stable mesalazine formulations like the eudragit-S coating of Asacol brand mesalazine and the Pentasa brand's encapsulation of mesalazine within microgranules 1. In the present day, contemporary research regarding novel methods to stabilize mesalazine continues and interest in the agent's capacity to decrease inflammatory activity and subsequently potentially reduce the risk of colorectal cancer in conditions like ulcerative colitis is maintained.1,2

Type
Small Molecule
Groups
Approved
Structure
Weight
Average: 153.1354
Monoisotopic: 153.042593095
Chemical Formula
C7H7NO3
Synonyms
  • 3-carboxy-4-hydroxyaniline
  • 5-aminosalicylic acid
  • 5-ASA
  • m-Aminosalicylic acid
  • Mesalamine
  • Mesalazina
  • Mésalazine
  • Mesalazine
  • Mesalazinum
  • p-Aminosalicylsaeure
External IDs
  • MAX-002
  • SPD476

Pharmacology

Indication

Mesalazine is indicated for the treatment of mildly to moderately active ulcerative colitis in adults and patients 5 years or older.16,15. Mesalazine is also indicated for the maintenance of remission of ulcerative colitis in adults and maintenance of remission of Crohn's ileocolitis.17,12

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Prevention ofCrohn's disease relapse••••••••••••••••••• ••••••• •••••••
Management ofCrohn's ileocolitis••••••••••••••••••• ••••••• •••••••
Management ofMild to moderate ulcerative colitis•••••••••••••••••••• ••• ••••••••••• •••••••• •••••••
Management ofMild to moderate ulcerative colitis••••••••••••••••••• ••••••• •••••••
Management ofProctitis••••••••••••••••••••••• ••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Mesalazine is one of the two components of sulphasalazine, the other being sulphapyridine. It is the latter responsible for most of the side effects associated with sulphasalazine therapy, while mesalazine is known to be the active moiety in the treatment of ulcerative colitis 12.

Mesalazine is thought to dampen the inflammatory process through its ability to inhibit prostaglandin synthesis, interfere with leukotriene synthesis, and consequent leukocyte migration as well as act as a potent scavenger of free radicals.25 Regardless of the mode of action, mesalazine appears to be active mainly topically rather than systemically.25

Intraperitoneally administered mesalazine at 30 and 340 mg/kg daily had similar efficacy in attenuating colitis as prednisolone 4 to 550 mg/kg daily given intraperitoneally or sulphasalazine 0.34 to 5 mg/kg given orally in immune complex-induced colitis mice.11 Mesalazine at 5 mmol/L and sulphasalazine 1.5 mmol/L also reversed the increase in water and chloride secretion and decrease the sodium in dinitrochlorbenzene-induced colitis guinea pig.11

Mechanism of action

Although the mechanism of action of mesalazine is not fully understood, it is believed to possess a topical anti-inflammatory effect on colonic epithelial cells.14 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.14

Furthermore, mesalazine also has the potential to inhibit the activation of Nuclear Factor kappa B (NFkB) and consequently the production of key pro-inflammatory cytokines.3,4,5 It has been proposed that reduced expression of PPAR gamma nuclear receptors (gamma form of peroxisome proliferator-activated receptors) may be implicated in ulcerative colitis, and that mesalazine produces pharmacodynamic effects through direct activation of PPAR gamma receptors in the colonic/rectal epithelium.9,6,7,8 Other research also showed the potential involvement of inducible NO synthase (iNOS) and that mesalazine can inhibit this enzyme to amiliorate the enteropathy in inflammatory bowel diseases.25

Moreover, since increased leukocyte migration, abnormal cytokine production, increased production of arachidonic acid metabolites, particularly leukotriene B4, and increased free radical formation in the inflamed intestinal tissue are all present in patients with inflammatory bowel disease it is also believed that mesalazine has in-vitro and in-vivo pharmacological effects that inhibit leukocyte chemotaxis, decrease cytokine and leukotriene production and scavenge for free radicals.13

TargetActionsOrganism
AProstaglandin G/H synthase 2
inhibitor
Humans
AProstaglandin G/H synthase 1
inhibitor
Humans
APolyunsaturated fatty acid 5-lipoxygenase
inhibitor
Humans
APeroxisome proliferator-activated receptor gamma
agonist
Humans
UInhibitor of nuclear factor kappa-B kinase subunit alpha
inhibitor
Humans
UInhibitor of nuclear factor kappa-B kinase subunit beta
inhibitor
Humans
UNitric oxide synthase, inducible
inhibitor
Humans
Absorption

Depending on the formulation administered, prescribing information for orally administered delayed-released tablets of 2.4g or 4.8g of mesalazine given once daily for 14 days to healthy volunteers was to found to be about 21% to 22% of the administered dose Label while prescribing information for an orally administered controlled-release capsule formulation suggests 20% to 30% of the mesalazine in the formulation is absorbed.27 In contrast, when mesalamine is administered orally as an unformulated 1-g aqueous suspension, mesalazine is approximately 80% absorbed.27

Volume of distribution

For the extended-release formulation, mesalazine has a Vd of 18 L, confirming minimal extravascular penetration of systemically available drug.18 For the delayed-release formulation, the apparent volume of distribution was estimated to be 4.8 L.19

Protein binding

In an in vitro study, at 2.5 mcg/mL, mesalamine and N-Ac-5-ASA are 43±6% and 78±1% bound, respectively, to plasma proteins. Protein binding of N-Ac-5-ASA does not appear to be concentration dependent at concentrations ranging from 1 to 10 mcg/mL.17

Metabolism

Mesalazine is metabolized both pre-systemically by the intestinal mucosa and systemically in the liver to N-acetyl-5-aminosalicylic acid (N-Ac-5-ASA) principally by NAT-1. Some acetylation also occurs through the action of colonic bacteria.13,17

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Route of elimination

Elimination of mesalazine is mainly via the renal route following metabolism to N-acetyl-5-aminosalicylic acid (acetylation) 23. However, there is also limited excretion of the parent mesalazine drug in the urine.23

After the oral administration of the extended-release formulation of mesalazine, of the approximately 21% to 22% of the drug absorbed, less than 8% of the dose was excreted unchanged in the urine after 24 hours, compared with greater than 13% for N-acetyl-5-aminosalicylic acid.23

When given the controlled-release formulation, about 130 mg free mesalazine was recovered in the feces following a single 1-g dose, which was comparable to the 140 mg of mesalazine recovered from the molar equivalent sulfasalazine tablet dose of 2.5 g F3001]. Elimination of free mesalazine and salicylates in feces increased proportionately with the dose given. N-acetylmesalazine was the primary compound excreted in the urine (19% to 30%) following the controlled-release dosing.27

In patients with ulcerative proctitis treated with mesalamine 500 mg as a rectal suppository every 8 hours for 6 days, 12% or less of the dose was eliminated in urine as unchanged 5-ASA and 8% to 77% was eliminated as N-acetyl-5-ASA following the initial dose. At steady state, 11% or less of the dose was eliminated in the urine as unchanged 5-ASA and 3% to 35% was eliminated as N-acetyl-5-ASA.16

Half-life

For the delayed-release formulation, after intravenous administration, the elimination half-life of mesalamine is reported to be approximately 40 minutes. After oral dosing, the median terminal half life values for mesalamine are usually about 25 hours, but are variable, ranging from 1.5 to 296 hours. There is a large inter-subject and intra-subject variability in the plasma concentrations of mesalamine and N-acetyl-5-aminosalicylic acid and in their terminal half-lives following the administration of mesalazine.15 For the extended-release formulation, following single and multiple doses of mesalazine, the mean half-lives were 9 to 10 hours for 5-ASA, and 12 to 14 hours for N-Ac-5-ASA.17

The mean elimination half-life was 5 hours (CV=73%) for 5-ASA and 5 hours (CV=63%) for N-acetyl-5-ASA in patients taking 500 mg mesalazine as a rectal suppository every 8 hours for 6 days.16 For the rectal enema suspension formulation, the elimination half-life was 0.5 to 1.5 hours for 5-ASA and 5 to 10 hours for N-acetyl-5-ASA.24

Clearance

The mean (SD) renal clearance in L/h for mesalazine following the single dose administration of mesalazine delayed-release tablets 4.8g under fasting conditions to young and elderly subjects were documented as 2.05 ± 1.33 in young subjects aged 18 to 35 years old, 2.04 ± 1.16 in elderly subjects aged 65 to 75 years old and 2.13 ± 1.20 in elderly subjects older than 75 years.23

Adverse Effects
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Toxicity

Mesalazine caused no increase in the incidence of neoplastic lesions over controls in a two-year study of Wistar rats fed up to 320 mg/kg/day of mesalazine admixed with diet (about 1.7 times the recommended human intra-rectal dose of CANASA, based on body surface area). Mesalazine was not mutagenic in the Ames test, the mouse lymphoma cell (TK+/-) forward mutation test, or the mouse micronucleus test. No effects on fertility or reproductive performance of the male and female rats were observed at oral mesalamine doses up to 320 mg/kg/day (about 1.7 times the recommended human intra-rectal dose of mesalazine, based on body surface area).16

Mesalazine is an aminosalicylate, and symptoms of salicylate toxicity include nausea, vomiting and abdominal pain, tachypnea, hyperpnea, tinnitus, and neurologic symptoms (headache, dizziness, confusion, seizures). Severe salicylate intoxication may lead to electrolyte and blood pH imbalance and potentially to other organ involvement (e.g., renal and liver). There is no specific antidote for mesalamine overdose; however, conventional therapy for salicylate toxicity may be beneficial in the event of acute overdosage and may include gastrointestinal tract decontamination to prevent further absorption. Correct fluid and electrolyte imbalance by the administration of appropriate intravenous therapy and maintain adequate renal function.14

Mesalazine is known to be substantially excreted by the kidney, and the risk of adverse reactions may be greater in patients with impaired renal function. Evaluate renal function in all patients prior to initiation and periodically while on Asacol HD therapy. Monitor patients with known renal impairment or a history of renal disease or taking nephrotoxic drugs for decreased renal function and mesalamine-related adverse reactions.14

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirMesalazine may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbciximabThe risk or severity of bleeding can be increased when Mesalazine is combined with Abciximab.
AcarboseMesalazine may increase the hypoglycemic activities of Acarbose.
AcebutololMesalazine may decrease the antihypertensive activities of Acebutolol.
AceclofenacThe risk or severity of nephrotoxicity can be increased when Mesalazine is combined with Aceclofenac.
Food Interactions
  • Take with or without food. The absorption is unaffected by food.

Products

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Product Images
International/Other Brands
Asacolitin / Claversal / Fisalamine / Iialda / Lixacol
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
5-asaTablet, delayed release400 mgOralSanis Health Inc2010-11-022012-08-03Canada flag
AprisoCapsule, extended release375 mg/1OralAphena Pharma Solutions - Tennessee, LLC2008-10-31Not applicableUS flag
AprisoCapsule, extended release375 mg/1OralSalix Pharmaceuticals2008-10-31Not applicableUS flag
AprisoCapsule, extended release375 mg/1OralPhysicians Total Care, Inc.2010-08-18Not applicableUS flag
AsacolTablet, delayed release400 mgOralAllergan, Inc.1993-12-312020-07-17Canada flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
MesalamineCapsule, extended release0.375 g/1OralAscend Laboratories, LLC2021-07-16Not applicableUS flag
MesalamineCapsule, extended release500 mg/1OralAmerican Health Packaging2023-01-20Not applicableUS flag
MesalamineTablet, delayed release1.2 g/1OralSun Pharmaceutical Industries (Europe) B.V.2019-02-01Not applicableUS flag
MesalamineSuppository1000 mg/1Rectalbryant ranch prepack2019-06-05Not applicableUS flag
MesalamineTablet, delayed release800 mg/1OralZydus Lifesciences Limited2018-08-02Not applicableUS flag

Categories

ATC Codes
A07EC02 — Mesalazine
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as aminobenzoic acids. These are benzoic acids containing an amine group attached to the benzene moiety.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzoic acids and derivatives
Direct Parent
Aminobenzoic acids
Alternative Parents
Salicylic acids / Benzoic acids / p-Aminophenols / Benzoyl derivatives / Aniline and substituted anilines / 1-hydroxy-2-unsubstituted benzenoids / Vinylogous acids / Amino acids / Monocarboxylic acids and derivatives / Carboxylic acids
show 5 more
Substituents
1-hydroxy-2-unsubstituted benzenoid / Amine / Amino acid / Amino acid or derivatives / Aminobenzoic acid / Aminophenol / Aniline or substituted anilines / Aromatic homomonocyclic compound / Benzoic acid / Benzoyl
show 17 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
monocarboxylic acid, phenols, aromatic amine, amino acid, monohydroxybenzoic acid (CHEBI:6775)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
4Q81I59GXC
CAS number
89-57-6
InChI Key
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)
IUPAC Name
5-amino-2-hydroxybenzoic acid
SMILES
NC1=CC(C(O)=O)=C(O)C=C1

References

Synthesis Reference

Thomas M. Parkinson, Joseph P. Brown, Robert E. Wingard, Jr., "Pharmaceutical preparations containing a polymeric agent for releasing 5-aminosalicylic acid or its salts into the gastrointestinal tract." U.S. Patent US4298595, issued January, 1975.

US4298595
General References
  1. Mayberry J: The history of 5-ASA compounds and their use in ulcerative colitis--trailblazing discoveries in gastroenterology. J Gastrointestin Liver Dis. 2013 Dec;22(4):375-7. [Article]
  2. Stolfi C, De Simone V, Pallone F, Monteleone G: Mechanisms of action of non-steroidal anti-inflammatory drugs (NSAIDs) and mesalazine in the chemoprevention of colorectal cancer. Int J Mol Sci. 2013 Sep 3;14(9):17972-85. doi: 10.3390/ijms140917972. [Article]
  3. 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. [Article]
  4. 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. [Article]
  5. 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. [Article]
  6. 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. doi: 10.1093/carcin/bgn118. Epub 2008 Jun 9. [Article]
  7. 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. [Article]
  8. 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. [Article]
  9. 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. [Article]
  10. Nandi J, Saud B, Zinkievich JM, Palma DT, Levine RA: 5-aminosalicylic acid improves indomethacin-induced enteropathy by inhibiting iNOS transcription in rats. Dig Dis Sci. 2008 Jan;53(1):123-32. Epub 2007 May 15. [Article]
  11. Brogden RN, Sorkin EM: Mesalazine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in chronic inflammatory bowel disease. Drugs. 1989 Oct;38(4):500-23. doi: 10.2165/00003495-198938040-00003. [Article]
  12. Electronic Medicines Compendium: Asacol (mesalazine) 400mg MR Tablets Monograph [Link]
  13. Electronic Medicines Compendium: Pentasa (Mesalazine) Sachet 2g Monograph [Link]
  14. FDA Approved Drug Products: Asacol HD (mesalamine) delayed-release tablets for oral use [Link]
  15. FDA Approved Drug Products: Delzicol (mesalamine) delayed-release capsules for oral use [Link]
  16. FDA Approved Drug Products: Canasa (mesalamine) suppositories for rectal use [Link]
  17. FDA Approved Drug Products: APRISO® (mesalamine) extended-release capsules [Link]
  18. Electronic Medicines Compendium: Mezavant XL 1200mg, gastro-resistant, prolonged release tablets [Link]
  19. Clinical Pharmacology Review : Asacol HD [Link]
  20. Mesalazine MSDS Pharmacopoeia [Link]
  21. Mesalazine MSDS Allergan [Link]
  22. Mesalazine MSDS USP [Link]
  23. FDA Approved Drug Products: LIALDA (mesalamine) delayed-release tablets, for oral use [Link]
  24. FDA Approved Drug Products: ROWASA (mesalamine) Rectal Suspension Enema [Link]
  25. Product Monograph: SALOFALK (mesalamine) delayed release tablets, for oral use [Link]
  26. FDA Approved Drug Products: Apriso (mesalamine) extended-release capsules for oral use [Link]
  27. Pentasa (Mesalazine) FDA Label [File]
Human Metabolome Database
HMDB0014389
KEGG Drug
D00377
PubChem Compound
4075
PubChem Substance
46509142
ChemSpider
3933
BindingDB
60918
RxNav
52582
ChEBI
6775
ChEMBL
CHEMBL704
ZINC
ZINC000000001688
Therapeutic Targets Database
DAP000729
PharmGKB
PA450384
Guide to Pharmacology
GtP Drug Page
RxList
RxList Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Mesalazine
FDA label
Download (1.61 MB)
MSDS
Download (67.7 KB)

Clinical Trials

Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package
PhaseStatusPurposeConditionsCountStart DateWhy Stopped100+ additional columns
Not AvailableCompletedNot AvailableDeficiency, Vitamin D / Ulcerative Colitis / Vitamin D Supplements1somestatusstop reasonjust information to hide
Not AvailableCompletedNot AvailableDistal Ulcerative Colitis1somestatusstop reasonjust information to hide
Not AvailableCompletedNot AvailableHidradenitis Suppurativa (HS)1somestatusstop reasonjust information to hide
Not AvailableCompletedNot AvailableInflammatory Bowel Diseases (IBD) / Psoriasis1somestatusstop reasonjust information to hide
Not AvailableCompletedNot AvailableUlcerative Colitis1somestatusstop reasonjust information to hide

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
  • Alaven Pharmaceutical
  • Amerisource Health Services Corp.
  • Anip Acquisition Co.
  • Atlantic Biologicals Corporation
  • Axcan Pharma Inc.
  • Cardinal Health
  • Comprehensive Consultant Services Inc.
  • Cosmo SPA
  • Dept Health Central Pharmacy
  • Diversified Healthcare Services Inc.
  • Ferring Pharmaceuticals Inc.
  • Franklin Pharmaceutical LLC
  • Gavis Pharmaceuticals LLC
  • Heartland Repack Services LLC
  • Infar SA
  • Letco Medical Inc.
  • Norwich Pharmaceuticals Inc.
  • Paddock Labs
  • PD-Rx Pharmaceuticals Inc.
  • Perrigo Co.
  • Physicians Total Care Inc.
  • Prasco Labs
  • Prepak Systems Inc.
  • Resource Optimization and Innovation LLC
  • Salix Pharmaceuticals
  • Sanofi-Aventis Inc.
  • Shire Inc.
  • Solvay Pharmaceuticals
  • Teva Pharmaceutical Industries Ltd.
  • Vangard Labs Inc.
  • Warner Chilcott Co. Inc.
  • WC Pharmaceuticals
  • Wellspring Pharmaceutical
Dosage Forms
FormRouteStrength
Capsule, extended releaseOral375 mg/1
Capsule, delayed releaseOral400 MG
Granule, for suspensionRectal2 G
SuspensionRectal2 G/50ML
SuspensionRectal4 G/50ML
SuspensionRectal4 G/100ML
TabletOral400 mg/1
Tablet, delayed releaseOral400 mg/1
Tablet, delayed releaseOral1600 MG
Tablet, delayed releaseOral
Tablet, delayed releaseOral800 mg/1
Tablet, coatedOral400 mg
Tablet, coatedOral800 mg
Aerosol, foamRectal2 G
Aerosol, foamRectal4 G
EnemaRectal2 G
EnemaRectal4 G
GelRectal500 MG
Granule, for suspensionRectal1.5 G
SuppositoryRectal400 MG
TabletOral400 MG
TabletOral800 MG
SuspensionRectal
GelRectal10 %
TabletOral1200.000 mg
Tablet, delayed releaseOral1000 mg
SuppositoryRectal1000 mg/1
SuppositoryRectal0.5 g
SuspensionRectal4 G/60G
Tablet, film coatedOral500 mg
Granule, delayed releaseOral1.5 G
Aerosol, foamRectal1 G
GranuleOral1.5 g
GranuleOral3 g
TabletOral250.000 mg
Capsule, delayed releaseOral400 mg/1
TabletOral1200.00 mg
SuppositoryRectal
Tablet, coatedOral
Tablet, delayed releaseOral1.2 g/1
SuspensionRectal6.67 g
Tablet, delayed releaseOral400 mg
SolutionRectal2 G
SolutionRectal4 G
Granule, delayed releaseOral1000 mg
Granule, delayed releaseOral1500 mg
Granule, delayed releaseOral3000 mg
Granule, delayed releaseOral500 mg
Capsule, extended releaseOral0.375 g/1
Capsule, extended releaseOral500 mg/1
Enema; kitRectal4 g/60mL
PowderNot applicable1 g/1g
SuspensionRectal4 g/60mL
Aerosol, foamRectal
GelRectal
PowderRectal
CapsuleOral400 MG
GelRectal2 G/60ML
GelRectal4 G/60ML
SuspensionRectal2 G
SuspensionRectal4 G
TabletOral1200 MG
Tablet, extended releaseOral1200 MG
SuspensionRectal7 g
Tablet, delayed releaseOral800 mg
SuspensionRectal6667 mg
Tablet, coatedOral505 mg
Tablet, extended releaseOral1.2 g
Tablet, delayed releaseOral1200 MG
Tablet, film coated, extended releaseOral
Tablet, delayed releaseOral1200.0 mg
KitRectal1 g / act
TabletOral500.000 mg
CapsuleOral250 mg/1
CapsuleOral500 mg/1
GranuleOral1 G
GranuleOral2.000 g
SuppositoryRectal1.000 g
SuspensionRectal1 G/100ML
SuspensionRectal1 g / 100 mL
SuspensionRectal2 G/100ML
SuspensionRectal4 g / 100 mL
TabletOral1 G
TabletOral250 MG
Tablet, extended releaseOral1 g
EnemaRectal1 g
EnemaRectal1 g/100ml
Tablet, extended releaseOral
SuppositoryRectal1.000 MG
SuspensionRectal1000 MG
Tablet, extended releaseOral50000000 mg
EnemaRectal
Enema; liquidRectal2 g / 100 mL
Tablet, extended releaseOral250 mg
SuspensionRectal1 g/100 ml
Granule, delayed releaseOral1 g
Granule, delayed releaseOral2000 mg
Granule, delayed releaseOral4000 mg
Tablet, extended releaseOral1000 mg
TabletOral1000 mg
TabletOral500 mg
SuspensionRectal0.01 g/ml
GranuleOral2 g
GranuleOral4 g
Granule, delayed releaseOral4 G
GranuleOral
SuppositoryRectal1 g
SuppositoryRectal1000 mg
Granule, delayed releaseOral2 G
SuspensionRectal1 g
GranuleOral2000 mg
GranuleOral200000000 mg
CapsuleOral
EnemaRectal4 g/60mL
EnemaRectal4 G/60G
GranuleOral1000.00 mg
SuppositoryRectal250.000 mg
SuspensionRectal2 g / 60 g
SuspensionRectal4 g / 60 g
SuspensionRectal4.0000 g
TabletOral
EmulsionRectal1 g
GranuleOral3000 mg
Tablet, delayed releaseOral1 G
SuppositoryRectal250 mg
Tablet, delayed releaseOral250 mg
Tablet, coatedOral250 mg
SuspensionRectal2 G/30ML
Tablet, delayed releaseOral500 mg
SuppositoryRectal500 mg
SuppositoryRectal50000000 mg
Tablet, coatedOral500 mg
GranuleOral500 mg/1sachet
Granule, delayed releaseOral3 G
GranuleOral1500 mg
GranuleOral1000 mg
SuspensionRectal400000 g
Tablet, delayed releaseOral50000000 mg
GranuleOral500 mg
SuspensionRectal6.667 g
TabletOral1600 MG
Tablet, extended releaseOral500 mg
Prices
Unit descriptionCostUnit
Canasa 30 1000 mg Suppository Box488.32USD box
Canasa 1000 mg suppository13.88USD suppository
Salofalk (4 g/60 g) 4 g/enm Enema6.73USD enema
Canasa 500 mg suppository6.24USD suppository
Pentasa (4 g/100 Ml) 4 g/enm Enema5.02USD enema
Pentasa (1 g/100Ml) 1 g/enm Enema4.17USD enema
Salofalk (2 g/60 g) 2 g/enm Enema3.96USD enema
Asacol hd dr 800 mg tablet3.88USD tablet
Pentasa 500 mg capsule2.66USD capsule
Asacol 400 mg Enteric Coated Tabs2.22USD tab
Asacol ec 400 mg tablet1.94USD tablet
Salofalk 1000 mg Suppository1.81USD suppository
Pentasa 1 g Suppository1.8USD suppository
Salofalk 500 mg Suppository1.23USD suppository
Asacol 800 800 mg Enteric-Coated Tablet1.14USD tablet
Pentasa 250 mg capsule1.07USD capsule
Mesasal 500 mg Enteric-Coated Tablet0.69USD tablet
Pentasa 500 mg Sustained-Release Tablet0.63USD tablet
Asacol 400 mg Enteric-Coated Tablet0.59USD tablet
Salofalk 500 mg Enteric-Coated Tablet0.56USD tablet
Novo-5 Asa 400 mg Enteric-Coated Tablet0.42USD tablet
Rowasa 4 gm/60 ml enema0.41USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5541170No1996-07-302013-07-30US flag
CA2444814No2009-06-092021-10-24Canada flag
CA2111697No2002-08-202012-06-16Canada flag
US7645801No2010-01-122027-07-24US flag
US6773720No2004-08-102020-06-08US flag
US8436051No2013-05-072028-06-06US flag
US8217083No2012-07-102028-06-06US flag
US6893662No2005-05-172021-11-15US flag
US8580302No2013-11-122021-11-15US flag
US9089492No2015-07-282021-11-15US flag
US8911778No2014-12-162018-04-20US flag
US6551620No2003-04-222018-04-20US flag
US8337886No2012-12-252018-04-20US flag
US8865688No2014-10-212030-05-01US flag
US8496965No2013-07-302018-04-20US flag
US8940328No2015-01-272018-04-20US flag
US8956647No2015-02-172018-04-20US flag
US6649180No2003-11-182020-04-13US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)260-280 °CL44306
water solubility0.84 g/L at 20°CL44296
Predicted Properties
PropertyValueSource
Water Solubility12.2 mg/mLALOGPS
logP0.75ALOGPS
logP-0.29Chemaxon
logS-1.1ALOGPS
pKa (Strongest Acidic)2.02Chemaxon
pKa (Strongest Basic)5.87Chemaxon
Physiological Charge-1Chemaxon
Hydrogen Acceptor Count4Chemaxon
Hydrogen Donor Count3Chemaxon
Polar Surface Area83.55 Å2Chemaxon
Rotatable Bond Count1Chemaxon
Refractivity40 m3·mol-1Chemaxon
Polarizability14.26 Å3Chemaxon
Number of Rings1Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9471
Blood Brain Barrier-0.6168
Caco-2 permeable-0.8829
P-glycoprotein substrateNon-substrate0.8186
P-glycoprotein inhibitor INon-inhibitor0.985
P-glycoprotein inhibitor IINon-inhibitor0.9912
Renal organic cation transporterNon-inhibitor0.9314
CYP450 2C9 substrateNon-substrate0.8284
CYP450 2D6 substrateNon-substrate0.8331
CYP450 3A4 substrateNon-substrate0.7636
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.8712
CYP450 2D6 inhibitorNon-inhibitor0.9744
CYP450 2C19 inhibitorInhibitor0.6752
CYP450 3A4 inhibitorNon-inhibitor0.6628
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9023
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.7922
BiodegradationReady biodegradable0.6197
Rat acute toxicity1.7065 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9759
hERG inhibition (predictor II)Non-inhibitor0.9715
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (8.48 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-0zg0-1900000000-8c59ef73371ab7058ab9
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0f79-0900000000-db75ae2d436dd6156c91
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-000i-0900000000-a6d526e6a554d5b9ba1f
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0bu9-2900000000-ce0399fca8bbf8131fe6
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4i-0900000000-b5f5476159ea4f18b25c
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4i-1900000000-64bddf687e410abdc939
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-001i-9100000000-0dc9c4162c675461d065
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0fbc-9100000000-6df4f9f138b1c49ec992
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-000i-0900000000-a6d526e6a554d5b9ba1f
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4i-0900000000-b5f5476159ea4f18b25c
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0bu9-2900000000-ce0399fca8bbf8131fe6
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4i-1900000000-64bddf687e410abdc939
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-001i-9100000000-0dc9c4162c675461d065
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0fbc-9100000000-6df4f9f138b1c49ec992
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-131.8545263
predicted
DarkChem Lite v0.1.0
[M-H]-131.6773263
predicted
DarkChem Lite v0.1.0
[M-H]-132.0126263
predicted
DarkChem Lite v0.1.0
[M-H]-128.3325
predicted
DeepCCS 1.0 (2019)
[M-H]-131.8545263
predicted
DarkChem Lite v0.1.0
[M-H]-131.6773263
predicted
DarkChem Lite v0.1.0
[M-H]-132.0126263
predicted
DarkChem Lite v0.1.0
[M-H]-128.3325
predicted
DeepCCS 1.0 (2019)
[M+H]+133.0074263
predicted
DarkChem Lite v0.1.0
[M+H]+133.2136263
predicted
DarkChem Lite v0.1.0
[M+H]+132.9304263
predicted
DarkChem Lite v0.1.0
[M+H]+131.64499
predicted
DeepCCS 1.0 (2019)
[M+H]+133.0074263
predicted
DarkChem Lite v0.1.0
[M+H]+133.2136263
predicted
DarkChem Lite v0.1.0
[M+H]+132.9304263
predicted
DarkChem Lite v0.1.0
[M+H]+131.64499
predicted
DeepCCS 1.0 (2019)
[M+Na]+132.1999263
predicted
DarkChem Lite v0.1.0
[M+Na]+132.1872263
predicted
DarkChem Lite v0.1.0
[M+Na]+132.1851263
predicted
DarkChem Lite v0.1.0
[M+Na]+141.11731
predicted
DeepCCS 1.0 (2019)
[M+Na]+132.1999263
predicted
DarkChem Lite v0.1.0
[M+Na]+132.1872263
predicted
DarkChem Lite v0.1.0
[M+Na]+132.1851263
predicted
DarkChem Lite v0.1.0
[M+Na]+141.11731
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Dual cyclooxygenase and peroxidase in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate, AA, C20:4(n-6)), with a particular role in the inflammatory response (PubMed:11939906, PubMed:16373578, PubMed:19540099, PubMed:22942274, PubMed:26859324, PubMed:27226593, PubMed:7592599, PubMed:7947975, PubMed:9261177). The cyclooxygenase activity oxygenates AA to the hydroperoxy endoperoxide prostaglandin G2 (PGG2), and the peroxidase activity reduces PGG2 to the hydroxy endoperoxide prostaglandin H2 (PGH2), the precursor of all 2-series prostaglandins and thromboxanes (PubMed:16373578, PubMed:22942274, PubMed:26859324, PubMed:27226593, PubMed:7592599, PubMed:7947975, PubMed:9261177). This complex transformation is initiated by abstraction of hydrogen at carbon 13 (with S-stereochemistry), followed by insertion of molecular O2 to form the endoperoxide bridge between carbon 9 and 11 that defines prostaglandins. The insertion of a second molecule of O2 (bis-oxygenase activity) yields a hydroperoxy group in PGG2 that is then reduced to PGH2 by two electrons (PubMed:16373578, PubMed:22942274, PubMed:26859324, PubMed:27226593, PubMed:7592599, PubMed:7947975, PubMed:9261177). Similarly catalyzes successive cyclooxygenation and peroxidation of dihomo-gamma-linoleate (DGLA, C20:3(n-6)) and eicosapentaenoate (EPA, C20:5(n-3)) to corresponding PGH1 and PGH3, the precursors of 1- and 3-series prostaglandins (PubMed:11939906, PubMed:19540099). In an alternative pathway of prostanoid biosynthesis, converts 2-arachidonoyl lysophopholipids to prostanoid lysophopholipids, which are then hydrolyzed by intracellular phospholipases to release free prostanoids (PubMed:27642067). Metabolizes 2-arachidonoyl glycerol yielding the glyceryl ester of PGH2, a process that can contribute to pain response (PubMed:22942274). Generates lipid mediators from n-3 and n-6 polyunsaturated fatty acids (PUFAs) via a lipoxygenase-type mechanism. Oxygenates PUFAs to hydroperoxy compounds and then reduces them to corresponding alcohols (PubMed:11034610, PubMed:11192938, PubMed:9048568, PubMed:9261177). Plays a role in the generation of resolution phase interaction products (resolvins) during both sterile and infectious inflammation (PubMed:12391014). Metabolizes docosahexaenoate (DHA, C22:6(n-3)) to 17R-HDHA, a precursor of the D-series resolvins (RvDs) (PubMed:12391014). As a component of the biosynthetic pathway of E-series resolvins (RvEs), converts eicosapentaenoate (EPA, C20:5(n-3)) primarily to 18S-HEPE that is further metabolized by ALOX5 and LTA4H to generate 18S-RvE1 and 18S-RvE2 (PubMed:21206090). In vascular endothelial cells, converts docosapentaenoate (DPA, C22:5(n-3)) to 13R-HDPA, a precursor for 13-series resolvins (RvTs) shown to activate macrophage phagocytosis during bacterial infection (PubMed:26236990). In activated leukocytes, contributes to oxygenation of hydroxyeicosatetraenoates (HETE) to diHETES (5,15-diHETE and 5,11-diHETE) (PubMed:22068350, PubMed:26282205). Can also use linoleate (LA, (9Z,12Z)-octadecadienoate, C18:2(n-6)) as substrate and produce hydroxyoctadecadienoates (HODEs) in a regio- and stereospecific manner, being (9R)-HODE ((9R)-hydroxy-(10E,12Z)-octadecadienoate) and (13S)-HODE ((13S)-hydroxy-(9Z,11E)-octadecadienoate) its major products (By similarity). During neuroinflammation, plays a role in neuronal secretion of specialized preresolving mediators (SPMs) 15R-lipoxin A4 that regulates phagocytic microglia (By similarity)
Specific Function
enzyme binding
Gene Name
PTGS2
Uniprot ID
P35354
Uniprot Name
Prostaglandin G/H synthase 2
Molecular Weight
68995.625 Da
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Dual cyclooxygenase and peroxidase that plays an important role in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate, AA, C20:4(n-6)), with a particular role in the inflammatory response. The cyclooxygenase activity oxygenates AA to the hydroperoxy endoperoxide prostaglandin G2 (PGG2), and the peroxidase activity reduces PGG2 to the hydroxy endoperoxide prostaglandin H2 (PGH2), the precursor of all 2-series prostaglandins and thromboxanes. This complex transformation is initiated by abstraction of hydrogen at carbon 13 (with S-stereochemistry), followed by insertion of molecular O2 to form the endoperoxide bridge between carbon 9 and 11 that defines prostaglandins. The insertion of a second molecule of O2 (bis-oxygenase activity) yields a hydroperoxy group in PGG2 that is then reduced to PGH2 by two electrons (PubMed:7947975). 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 (Probable). Can also use linoleate (LA, (9Z,12Z)-octadecadienoate, C18:2(n-6)) as substrate and produce hydroxyoctadecadienoates (HODEs) in a regio- and stereospecific manner, being (9R)-HODE ((9R)-hydroxy-(10E,12Z)-octadecadienoate) and (13S)-HODE ((13S)-hydroxy-(9Z,11E)-octadecadienoate) its major products (By similarity)
Specific Function
heme binding
Gene Name
PTGS1
Uniprot ID
P23219
Uniprot Name
Prostaglandin G/H synthase 1
Molecular Weight
68685.82 Da
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. [Article]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  3. Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Catalyzes the oxygenation of arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate) to 5-hydroperoxyeicosatetraenoate (5-HPETE) followed by the dehydration to 5,6- epoxyeicosatetraenoate (Leukotriene A4/LTA4), the first two steps in the biosynthesis of leukotrienes, which are potent mediators of inflammation (PubMed:19022417, PubMed:21233389, PubMed:22516296, PubMed:23246375, PubMed:24282679, PubMed:24893149, PubMed:31664810, PubMed:8615788, PubMed:8631361). Also catalyzes the oxygenation of arachidonate into 8-hydroperoxyicosatetraenoate (8-HPETE) and 12-hydroperoxyicosatetraenoate (12-HPETE) (PubMed:23246375). Displays lipoxin synthase activity being able to convert (15S)-HETE into a conjugate tetraene (PubMed:31664810). Although arachidonate is the preferred substrate, this enzyme can also metabolize oxidized fatty acids derived from arachidonate such as (15S)-HETE, eicosapentaenoate (EPA) such as (18R)- and (18S)-HEPE or docosahexaenoate (DHA) which lead to the formation of specialized pro-resolving mediators (SPM) lipoxin and resolvins E and D respectively, therefore it participates in anti-inflammatory responses (PubMed:17114001, PubMed:21206090, PubMed:31664810, PubMed:32404334, PubMed:8615788). Oxidation of DHA directly inhibits endothelial cell proliferation and sprouting angiogenesis via peroxisome proliferator-activated receptor gamma (PPARgamma) (By similarity). It does not catalyze the oxygenation of linoleic acid and does not convert (5S)-HETE to lipoxin isomers (PubMed:31664810). In addition to inflammatory processes, it participates in dendritic cell migration, wound healing through an antioxidant mechanism based on heme oxygenase-1 (HO-1) regulation expression, monocyte adhesion to the endothelium via ITGAM expression on monocytes (By similarity). Moreover, it helps establish an adaptive humoral immunity by regulating primary resting B cells and follicular helper T cells and participates in the CD40-induced production of reactive oxygen species (ROS) after CD40 ligation in B cells through interaction with PIK3R1 that bridges ALOX5 with CD40 (PubMed:21200133). May also play a role in glucose homeostasis, regulation of insulin secretion and palmitic acid-induced insulin resistance via AMPK (By similarity). Can regulate bone mineralization and fat cell differentiation increases in induced pluripotent stem cells (By similarity)
Specific Function
arachidonate 12(S)-lipoxygenase activity
Gene Name
ALOX5
Uniprot ID
P09917
Uniprot Name
Polyunsaturated fatty acid 5-lipoxygenase
Molecular Weight
77982.595 Da
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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General 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 pro-inflammatory responses. Plays a role in the regulation of cardiovascular circadian rhythms by regulating the transcription of BMAL1 in the blood vessels (By similarity)
Specific Function
alpha-actinin binding
Gene Name
PPARG
Uniprot ID
P37231
Uniprot Name
Peroxisome proliferator-activated receptor gamma
Molecular Weight
57619.58 Da
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. [Article]
  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. doi: 10.1093/carcin/bgn118. Epub 2008 Jun 9. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses (PubMed:18626576, PubMed:9244310, PubMed:9252186, PubMed:9346484). Acts as a part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B on serine residues (PubMed:18626576, PubMed:35952808, PubMed:9244310, PubMed:9252186, PubMed:9346484). These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome (PubMed:18626576, PubMed:9244310, PubMed:9252186, PubMed:9346484). In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis (PubMed:18626576, PubMed:9244310, PubMed:9252186, PubMed:9346484). Negatively regulates the pathway by phosphorylating the scaffold protein TAXBP1 and thus promoting the assembly of the A20/TNFAIP3 ubiquitin-editing complex (composed of A20/TNFAIP3, TAX1BP1, and the E3 ligases ITCH and RNF11) (PubMed:21765415). Therefore, CHUK plays a key role in the negative feedback of NF-kappa-B canonical signaling to limit inflammatory gene activation. As part of the non-canonical pathway of NF-kappa-B activation, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 and the formation of NF-kappa-B RelB-p52 complexes (PubMed:20501937). In turn, these complexes regulate genes encoding molecules involved in B-cell survival and lymphoid organogenesis. Participates also in the negative feedback of the non-canonical NF-kappa-B signaling pathway by phosphorylating and destabilizing MAP3K14/NIK. Within the nucleus, phosphorylates CREBBP and consequently increases both its transcriptional and histone acetyltransferase activities (PubMed:17434128). Modulates chromatin accessibility at NF-kappa-B-responsive promoters by phosphorylating histones H3 at 'Ser-10' that are subsequently acetylated at 'Lys-14' by CREBBP (PubMed:12789342). Additionally, phosphorylates the CREBBP-interacting protein NCOA3. Also phosphorylates FOXO3 and may regulate this pro-apoptotic transcription factor (PubMed:15084260). Phosphorylates RIPK1 at 'Ser-25' which represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death (By similarity). Phosphorylates AMBRA1 following mitophagy induction, promoting AMBRA1 interaction with ATG8 family proteins and its mitophagic activity (PubMed:30217973)
Specific Function
ATP binding
Gene Name
CHUK
Uniprot ID
O15111
Uniprot Name
Inhibitor of nuclear factor kappa-B kinase subunit alpha
Molecular Weight
84638.88 Da
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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses (PubMed:20434986, PubMed:20797629, PubMed:21138416, PubMed:30337470, PubMed:9346484). Acts as a part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation (PubMed:9346484). Phosphorylates inhibitors of NF-kappa-B on 2 critical serine residues (PubMed:20434986, PubMed:20797629, PubMed:21138416, PubMed:9346484). These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome (PubMed:20434986, PubMed:20797629, PubMed:21138416, PubMed:9346484). In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis (PubMed:20434986, PubMed:20797629, PubMed:21138416, PubMed:9346484). In addition to the NF-kappa-B inhibitors, phosphorylates several other components of the signaling pathway including NEMO/IKBKG, NF-kappa-B subunits RELA and NFKB1, as well as IKK-related kinases TBK1 and IKBKE (PubMed:11297557, PubMed:14673179, PubMed:20410276, PubMed:21138416). IKK-related kinase phosphorylations may prevent the overproduction of inflammatory mediators since they exert a negative regulation on canonical IKKs (PubMed:11297557, PubMed:20410276, PubMed:21138416). Phosphorylates FOXO3, mediating the TNF-dependent inactivation of this pro-apoptotic transcription factor (PubMed:15084260). Also phosphorylates other substrates including NAA10, NCOA3, BCL10 and IRS1 (PubMed:17213322, PubMed:19716809). Phosphorylates RIPK1 at 'Ser-25' which represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death (By similarity). Phosphorylates the C-terminus of IRF5, stimulating IRF5 homodimerization and translocation into the nucleus (PubMed:25326418). Following bacterial lipopolysaccharide (LPS)-induced TLR4 endocytosis, phosphorylates STAT1 at 'Thr-749' which restricts interferon signaling and anti-inflammatory responses and promotes innate inflammatory responses (PubMed:38621137). IKBKB-mediated phosphorylation of STAT1 at 'Thr-749' promotes binding of STAT1 to the ARID5A promoter, resulting in transcriptional activation of ARID5A and subsequent ARID5A-mediated stabilization of IL6 (PubMed:32209697). It also promotes binding of STAT1 to the IL12B promoter and activation of IL12B transcription (PubMed:32209697)
Specific Function
ATP binding
Gene Name
IKBKB
Uniprot ID
O14920
Uniprot Name
Inhibitor of nuclear factor kappa-B kinase subunit beta
Molecular Weight
86563.245 Da
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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body (PubMed:7504305, PubMed:7531687, PubMed:7544004, PubMed:7682706). In macrophages, NO mediates tumoricidal and bactericidal actions. Also has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such PTGS2/COX2 (By similarity). As component of the iNOS-S100A8/9 transnitrosylase complex involved in the selective inflammatory stimulus-dependent S-nitrosylation of GAPDH on 'Cys-247' implicated in regulation of the GAIT complex activity and probably multiple targets including ANXA5, EZR, MSN and VIM (PubMed:25417112). Involved in inflammation, enhances the synthesis of pro-inflammatory mediators such as IL6 and IL8 (PubMed:19688109)
Specific Function
arginine binding
Gene Name
NOS2
Uniprot ID
P35228
Uniprot Name
Nitric oxide synthase, inducible
Molecular Weight
131116.3 Da
References
  1. Nandi J, Saud B, Zinkievich JM, Palma DT, Levine RA: 5-aminosalicylic acid improves indomethacin-induced enteropathy by inhibiting iNOS transcription in rats. Dig Dis Sci. 2008 Jan;53(1):123-32. Epub 2007 May 15. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Participates in the detoxification of a plethora of hydrazine and arylamine drugs. Catalyzes the N- or O-acetylation of various arylamine and heterocyclic amine substrates and is able to bioactivate several known carcinogens
Specific Function
arylamine N-acetyltransferase activity
Gene Name
NAT1
Uniprot ID
P18440
Uniprot Name
Arylamine N-acetyltransferase 1
Molecular Weight
33898.445 Da
References
  1. Mesalazine FDA Label [File]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Mediates the Na(+)-independent uptake of organic anions (PubMed:10358072, PubMed:15159445, PubMed:17412826). Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (dehydroepiandrosterone 3-sulfate, 17-beta-glucuronosyl estradiol, and estrone 3-sulfate), as well as eicosanoids (prostaglandin E2, thromboxane B2, leukotriene C4, and leukotriene E4), and thyroid hormones (T4/L-thyroxine, and T3/3,3',5'-triiodo-L-thyronine) (PubMed:10358072, PubMed:10601278, PubMed:10873595, PubMed:11159893, PubMed:12196548, PubMed:12568656, PubMed:15159445, PubMed:15970799, PubMed:16627748, PubMed:17412826, PubMed:19129463, PubMed:26979622). Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop (PubMed:22232210). Involved in the clearance of endogenous and exogenous substrates from the liver (PubMed:10358072, PubMed:10601278). Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition (PubMed:26383540). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins), such as pravastatin and pitavastatin, a clinically important class of hypolipidemic drugs (PubMed:10601278, PubMed:15159445, PubMed:15970799). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drug methotrexate (PubMed:23243220). May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver (PubMed:16624871, PubMed:16627748). Shows a pH-sensitive substrate specificity towards prostaglandin E2 and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463)
Specific Function
bile acid transmembrane transporter activity
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. Konig J, Glaeser H, Keiser M, Mandery K, Klotz U, Fromm MF: Role of organic anion-transporting polypeptides for cellular mesalazine (5-aminosalicylic acid) uptake. Drug Metab Dispos. 2011 Jun;39(6):1097-102. doi: 10.1124/dmd.110.034991. Epub 2011 Mar 23. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Mediates the Na(+)-independent uptake of organic anions (PubMed:10779507, PubMed:15159445, PubMed:17412826). Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (17-beta-glucuronosyl estradiol, dehydroepiandrosterone sulfate (DHEAS), and estrone 3-sulfate), as well as eicosanoid leukotriene C4, prostaglandin E2 and L-thyroxine (T4) (PubMed:10779507, PubMed:11159893, PubMed:12568656, PubMed:15159445, PubMed:17412826, PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463). Shows a pH-sensitive substrate specificity towards sulfated steroids, taurocholate and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:19129463). Involved in the clearance of bile acids and organic anions from the liver (PubMed:22232210). Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop (PubMed:22232210). Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition (PubMed:26383540). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins) such as pitavastatin, a clinically important class of hypolipidemic drugs (PubMed:15159445). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drugs methotrexate and paclitaxel (PubMed:23243220). May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver (PubMed:16624871, PubMed:16627748)
Specific Function
bile acid transmembrane transporter activity
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da
References
  1. Konig J, Glaeser H, Keiser M, Mandery K, Klotz U, Fromm MF: Role of organic anion-transporting polypeptides for cellular mesalazine (5-aminosalicylic acid) uptake. Drug Metab Dispos. 2011 Jun;39(6):1097-102. doi: 10.1124/dmd.110.034991. Epub 2011 Mar 23. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Mediates the Na(+)-independent transport of steroid sulfate conjugates and other specific organic anions (PubMed:10873595, PubMed:11159893, PubMed:11932330, PubMed:12724351, PubMed:14610227, PubMed:16908597, PubMed:18501590, PubMed:20507927, PubMed:22201122, PubMed:23531488, PubMed:25132355, PubMed:26383540, PubMed:27576593, PubMed:28408210, PubMed:29871943, PubMed:34628357). Responsible for the transport of estrone 3-sulfate (E1S) through the basal membrane of syncytiotrophoblast, highlighting a potential role in the placental absorption of fetal-derived sulfated steroids including the steroid hormone precursor dehydroepiandrosterone sulfate (DHEA-S) (PubMed:11932330, PubMed:12409283). Also facilitates the uptake of sulfated steroids at the basal/sinusoidal membrane of hepatocytes, therefore accounting for the major part of organic anions clearance of liver (PubMed:11159893). Mediates the intestinal uptake of sulfated steroids (PubMed:12724351, PubMed:28408210). Mediates the uptake of the neurosteroids DHEA-S and pregnenolone sulfate (PregS) into the endothelial cells of the blood-brain barrier as the first step to enter the brain (PubMed:16908597, PubMed:25132355). Also plays a role in the reuptake of neuropeptides such as substance P/TAC1 and vasoactive intestinal peptide/VIP released from retinal neurons (PubMed:25132355). May act as a heme transporter that promotes cellular iron availability via heme oxygenase/HMOX2 and independently of TFRC (PubMed:35714613). Also transports heme by-product coproporphyrin III (CPIII), and may be involved in their hepatic disposition (PubMed:26383540). Mediates the uptake of other substrates such as prostaglandins D2 (PGD2), E1 (PGE1) and E2 (PGE2), taurocholate, L-thyroxine, leukotriene C4 and thromboxane B2 (PubMed:10873595, PubMed:14610227, PubMed:19129463, PubMed:29871943, Ref.25). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable). Shows a pH-sensitive substrate specificity which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:14610227, PubMed:19129463, PubMed:22201122). The exact transport mechanism has not been yet deciphered but most likely involves an anion exchange, coupling the cellular uptake of organic substrate with the efflux of an anionic compound (PubMed:19129463, PubMed:20507927, PubMed:26277985). Hydrogencarbonate/HCO3(-) acts as a probable counteranion that exchanges for organic anions (PubMed:19129463). Cytoplasmic glutamate may also act as counteranion in the placenta (PubMed:26277985). An inwardly directed proton gradient has also been proposed as the driving force of E1S uptake with a (H(+):E1S) stoichiometry of (1:1) (PubMed:20507927)
Specific Function
bile acid transmembrane transporter activity
Gene Name
SLCO2B1
Uniprot ID
O94956
Uniprot Name
Solute carrier organic anion transporter family member 2B1
Molecular Weight
76697.93 Da
References
  1. Konig J, Glaeser H, Keiser M, Mandery K, Klotz U, Fromm MF: Role of organic anion-transporting polypeptides for cellular mesalazine (5-aminosalicylic acid) uptake. Drug Metab Dispos. 2011 Jun;39(6):1097-102. doi: 10.1124/dmd.110.034991. Epub 2011 Mar 23. [Article]

Drug created at June 13, 2005 13:24 / Updated at November 05, 2024 18:59