Repositioning Candidate Details
| Candidate ID: | R0093 |
| Source ID: | DB00244 |
| Source Type: | approved |
| Compound Type: | small molecule |
| Compound Name: | Mesalazine |
| Synonyms: | 3-carboxy-4-hydroxyaniline; 5-aminosalicylic acid; 5-ASA; m-Aminosalicylic acid; Mesalamine; Mesalazine |
| Molecular Formula: | C7H7NO3 |
| SMILES: | NC1=CC(C(O)=O)=C(O)C=C1 |
| Structure: |
|
| DrugBank Description: | 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 . It is considered to be the active moiety of sulphasalazine. (From Martindale, The Extra Pharmacopoeia, 30th ed) 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 . 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 . 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. |
| CAS Number: | 89-57-6 |
| Molecular Weight: | 153.1354 |
| DrugBank 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 , . Prescribing information for mesalazine in the UK also indicates the medication for the maintenance of remission of Crohn's ileo-colitis . |
| DrugBank Pharmacology: | 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 . The pharmacodynamic actions of mesalazine occur in the colonic/rectal mucosae local to the delivery of drug from mesalazine tablets into the lumen . 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 . Plasma concentrations representing systemically absorbed mesalazine are not believed to contribute extensively to efficacy . |
| DrugBank 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 . 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 . 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 . 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 . There is evidence that mesalazine produces pharmacodynamic effects through direct activation of PPAR gamma receptors in the colonic/rectal epithelium as well . 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 . |
| Targets: | Prostaglandin G/H synthase 2 inhibitor; Prostaglandin G/H synthase 1 inhibitor; Arachidonate 5-lipoxygenase inhibitor; Peroxisome proliferator-activated receptor gamma agonist; Inhibitor of nuclear factor kappa-B kinase subunit alpha inhibitor; Inhibitor of nuclear factor kappa-B kinase subunit beta inhibitor; Myeloperoxidase |
| Inclusion Criteria: | Therapeutic strategy associated |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs | |
|---|---|---|---|---|---|
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class |
|---|