General
Preferred name
mesalazine
Synonyms
MESALAMINE ()
5-Aminosalicylic acid ()
5-ASA ()
MESALAMINE HYDROCHLORIDE ()
5-Amino-2-hydroxy-benzoic acid89-57-6 ()
5-Aminosalicylic acid, 5-ASA, Mesalazine, Apriso, Asacol, Pentasa, Canasa ()
Mesalamine (5-ASA) ()
Sfrowasa ()
Fisalamine ()
Pentasa SR ()
Benzoic acid, 5-amino-2-hydroxy- ()
Canasa ()
Mesren MR ()
Delzicol ()
Iialda ()
Mezavant XL ()
NSC-38877 ()
Asacol ()
Mesalazine ()
Asacol Hd ()
Salofalk ()
Rowasa ()
Octasa ()
Lialda ()
Pentasa ()
Mesalazina ()
Coltec EC ()
MAX-002 ()
Ipocol ()
Apriso ()
5-aminosalicylate ()
5-Aminosalicylic Acid-d7 ()
P&D ID
PD000235
CAS
89-57-6
61513-32-4
1261398-47-3
6291-36-7
Tags
available
drug
Approved by
FDA
First approval
1987
Drug indication
Colitis
Ulcerative colitis
Drug Status
approved
Max Phase
4.0
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
METABOLISM
The primary metabolite of mesalazine (5-aminosalicylic acid) is predominantly N-acetyl-5-aminosalicylic acid (Ac-5-ASA) [FDA Label]. This metabolite is generated via N-acetyltransferase (NAT) activity in the liver and intestinal mucosa cells, largely by NAT-1, in particular [FDA Label].
PHARMACODYNAMICS
Mesalazine is one of the two components of sulphasalazine, the other being sulphapyridine. It is the latter which is responsible for the majority of the side effects associated with sulphasalazine therapy whilst mesalazine is known to be the active moiety in the treatment of ulcerative colitis [L5101]. The pharmacodynamic actions of mesalazine occur in the colonic/rectal mucosae local to the delivery of drug from mesalazine tablets into the lumen [FDA Label]. There is information suggesting that the severity of colonic inflammation in ulcerative colitis patients treated with mesalazine is inversely correlated with mucosal concentrations of mesalazine [FDA Label]. Plasma concentrations representing systemically absorbed mesalazine are not believed to contribute extensively to efficacy [FDA Label].
INDICATION
Mesalazine is indicated for the induction of remission in patients with active or mild to moderate acute exacerbations of ulcerative colitis and for the maintenance of remission of ulcerative colitis [FDA Label], [L5101]. Prescribing information for mesalazine in the UK also indicates the medication for the maintenance of remission of Crohn's ileo-colitis [L5101].
TOXICITY
Oral, mouse: LD50 = 3370 mg/kg; Oral, rat: LD50 = 2800 mg/kg; Skin, rabbit: LD50 = >5 gm/kg [MSDS]. 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. Although there is little to no clinical experience with mesalazine overdosage [FDA Label]. Mesalazine is an aminosalicylate, and symptoms of salicylate toxicity may be possible, such as tinnitus, vertigo, headache, confusion, drowsiness, sweating, hyperventilation, vomiting, and diarrhea [FDA Label]. Severe intoxication with salicylates can lead to disruption of electrolyte balance and blood-pH, hyperthermia, and dehydration [FDA Label].
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 [FDA Label] while prescribing information for an orally administered controlled-release capsule formulation suggests 20% to 30% of the mesalazine in the formulation is absorbed [F3001]. In contrast, when mesalamine is administered orally as an unformulated 1-g aqueous suspension, mesalazine is approximately 80% absorbed [F3001].
HALF-LIFE
The apparent elimination half-life documented for oral delayed-release mesalazine tablets is 7 to 12 hours [L5122]. The elimination half-life recorded for the active N-acetyl-5-aminosalicylic acid metabolite generated from the administration of oral delayed-release mesalazine tablets is 12 to 23 hours [L5122].
PHARMACODYNAMICS
Mesalazine is one of the two components of sulphasalazine, the other being sulphapyridine. It is the latter which is responsible for the majority of the side effects associated with sulphasalazine therapy whilst mesalazine is known to be the active moiety in the treatment of ulcerative colitis [L5101].; ; The pharmacodynamic actions of mesalazine occur in the colonic/rectal mucosae local to the delivery of drug from mesalazine tablets into the lumen [FDA Label]. There is information suggesting that the severity of colonic inflammation in ulcerative colitis patients treated with mesalazine is inversely correlated with mucosal concentrations of mesalazine [FDA Label]. Plasma concentrations representing systemically absorbed mesalazine are not believed to contribute extensively to efficacy [FDA Label].
TOXICITY
Oral, mouse: LD50 = 3370 mg/kg; Oral, rat: LD50 = 2800 mg/kg; Skin, rabbit: LD50 = >5 gm/kg [MSDS].; ; 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. Although there is little to no clinical experience with mesalazine overdosage [FDA Label]. Mesalazine is an aminosalicylate, and symptoms of salicylate toxicity may be possible, such as tinnitus, vertigo, headache, confusion, drowsiness, sweating, hyperventilation, vomiting, and diarrhea [FDA Label]. Severe intoxication with salicylates can lead to disruption of electrolyte balance and blood-pH, hyperthermia, and dehydration [FDA Label].
DESCRIPTION
Mesalazine is an aminosalicylate anti-inflammatory drug.
(GtoPdb)
MOA
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 [FDA Label]. 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 [FDA Label]. Furthermore, mesalazine also has the potential to inhibit the activation of Nuclear Factor kappa B (NKkB) and consequently the production of key of pro-inflammatory cytokines [FDA Label]. 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 [FDA Label]. There is evidence that mesalazine produces pharmacodynamic effects through direct activation of PPAR gamma receptors in the colonic/rectal epithelium as well [FDA Label]. 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 [L5107].
ROE
Elimination of mesalazine is mainly via the renal route following metabolism to N-acetyl-5-aminosalicylic acid (acetylation) [FDA Label]. However, there is also limited excretion of the parent mesalazine drug in the urine [FDA Label]. 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 [FDA Label]. 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 [F3001].
MOA
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 [FDA Label]. 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 [FDA Label].; ; Furthermore, mesalazine also has the potential to inhibit the activation of Nuclear Factor kappa B (NKkB) and consequently the production of key of pro-inflammatory cytokines [FDA Label]. 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 [FDA Label]. There is evidence that mesalazine produces pharmacodynamic effects through direct activation of PPAR gamma receptors in the colonic/rectal epithelium as well [FDA Label].; ; 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 [L5107].
ROE
Elimination of mesalazine is mainly via the renal route following metabolism to N-acetyl-5-aminosalicylic acid (acetylation) [FDA Label]. However, there is also limited excretion of the parent mesalazine drug in the urine [FDA Label].; ; 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 [FDA Label].; ; 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 [F3001].
PRICE
29
DESCRIPTION
This is the anion of the approved anti-inflammatory drug mesalazine (also known by the United States adopted name (USAN) mesalamine). Clinical information is curated on the ligand page.
(GtoPdb)
DESCRIPTION
Mesalazine is an anti-inflammatory agent, structurally related to the salicylates and non-steroidal anti-inflammatory drugs like acetylsalicylic acid, which is active in inflammatory bowel diseaseis.It is used to treat mild to moderate active ulcerative colitis and also to maintain remission once achieved.
(Enamine Bioactive Compounds)
DESCRIPTION
5-Aminosalicylic Acid (5-ASA) is 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.
(TargetMol Bioactive Compound Library)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Compound Sets
32
CeMM library of unique drugs (CLOUD)
ChEMBL Approved Drugs
ChEMBL Drugs
Concise Guide to Pharmacology 2017/18
Concise Guide to Pharmacology 2019/20
Concise Guide to Pharmacology 2021/22
Concise Guide to Pharmacology 2023/24
CZ-OPENSCREEN Bioactive Library
Drug Repurposing Hub
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMAP Approved Drugs
DrugMatrix
Enamine Bioactive Compounds
Enamine BioReference Compounds
Ki Database
LSP-MoA library (Laboratory of Systems Pharmacology)
MedChem Express Bioactive Compound Library
NCATS Inxight Approved Drugs
NIH Clinical Collections (NCC)
Novartis Chemogenetic Library (NIBR MoA Box)
NPC Screening Collection
Prestwick Chemical Library
ReFrame library
Selleckchem Bioactive Compound Library
TargetMol Bioactive Compound Library
The Spectrum Collection
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
79
Molecular Weight
153.04
Hydrogen Bond Acceptors
3
Hydrogen Bond Donors
3
Rotatable Bonds
1
Ring Count
1
Aromatic Ring Count
1
cLogP
0.67
TPSA
83.55
Fraction CSP3
0.0
Chiral centers
0.0
Largest ring
6.0
QED
0.41
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Pathway
NF-¦ÊB
NF-??
Cytoskeletal Signaling
DNA Damage/DNA Repair
Immunology/Inflammation
Metabolism
Neuroscience
Cell Cycle/DNA Damage
cytoskeleton
Metabolic Enzyme/Protease
Vitamin D Related/Nuclear Receptor
MOA
Unknown molecular target
Non-Steroidal Antiinflammatory Drugs
PPAR Gamma Inhibitor
cyclooxygenase inhibitor, lipoxygenase inhibitor, prostanoid receptor antagonist
Target
cyclooxygenase
ALOX5
COX
Endogenous Metabolite
MPO
NF-κB
PAK
PPAR
PPARγ
I??/IKK
ALOX5, CHUK, IKBKB, MPO, PPARG, PTGS1, PTGS2
Immunology & Inflammation related,I¦ÊB/IKK
Member status
virtual
Indication
ulcerative colitis, inflammatory bowel disease
Therapeutic Class
Antiinflammatory Agents
Source data
