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Identification
- Summary
Olsalazine is an anti-inflammatory aminosalicylate used in the treatment of inflammatory bowel disease and ulcerative colitis.
- Brand Names
- Dipentum
- Generic Name
- Olsalazine
- DrugBank Accession Number
- DB01250
- Background
Olsalazine is an aminosalicylate and a prodrug of mesalamine (5-aminosalicylic acid, 5-ASA).1 It was first developed for delivering mesalamine to the colon without the use of sulfapyridine.2 Olsalazine comprises two mesalamine molecules joined by an azo bridge, which is cleaved in the colon.2 Olsalazine is an anti-inflammatory agent that works by inhibiting cyclooxygenase and lipoxygenase, subsequently reducing the production of pro-inflammatory factors like prostaglandin and leukotriene.1 Olsalazine is used in the treatment of ulcerative colitis.5,6
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Olsalazine (DB01250)
- Weight
- Average: 302.239
Monoisotopic: 302.053886062 - Chemical Formula
- C14H10N2O6
- Synonyms
- Olsalazine
Pharmacology
- Indication
In the US, olsalazine is indicated for the maintenance of remission of ulcerative colitis in adult patients who are intolerant to sulfasalazine.5
In Canada, it is used in the treatment of acute ulcerative colitis of mild to moderate severity, with or without the concomitant use of steroids. It is also indicated for the long-term maintenance of patients with ulcerative colitis in remission.6
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Ulcerative colitis •••••••••••• ••••• ••••••••• ••••••• Management of Ulcerative colitis •••••••••••• ••••• ••••••• Adjunct therapy in management of Mild acute ulcerative colitis •••••••••••• ••••• ••••••• Management of Mild acute ulcerative colitis •••••••••••• ••••• ••••••• Management of Moderate acute ulcerative colitis •••••••••••• ••••• ••••••• - Contraindications & Blackbox Warnings
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Olsalazine is an anti-inflammatory agent that blocks the production of cyclooxygenase (COX)-derived products of arachidonic acid metabolism.5 It works to alleviate inflammation in ulcerative colitis.1
Olsalazine was shown to decrease water and sodium absorption. While olsalazine is not expected to affect the motility and transit time of small intestines, it decreased small bowel transit time at high doses ranging from 60 to 120 mg/kg. In about 40% of the patients with ulcerative colitis, administration of olsalazine 1g daily was associated with a decrease in whole gut transit time.1
- Mechanism of action
Upon administration, the azo bond connecting two molecules of mesalamine (also known as 5-aminosalicylic acid or 5-ASA) is cleaved by azoreductase-containing bacteria in the colon. The two molecules of mesalamine are released to mediate therapeutic effects.1 The exact mechanism of action of olsalazine and its active moiety mesalamine in ulcerative colitis has not been elucidated; however, it is understood that mesalamine mediates an anti-inflammatory action on epithelial cells of the colon.5 The COX-derived (i.e., prostanoids such as prostaglandin E2) and lipoxygenase-derived products (i.e., leukotrienes [LTs] and hydroxyeicosatetraenoic acids [HETEs]) of arachidonic acid metabolism have been implicated in the pathogenesis and maintenance of inflammatory disorders, including ulcerative colitis and inflammatory bowel disease.1,5 Mesalamine may attenuate inflammation by blocking the COX enzyme and inhibiting prostaglandin production in the colon.3,4,5 Olsalazine was also shown to inhibit xanthine oxidase, an enzyme that generates oxygen-derived free radicals.2
Olsalazine may attenuate intestinal inflammation by limiting macrophage migration to inflamed intestinal mucosa: it was shown to inhibit in vitro migration of intestinal macrophages in response to leukotriene B4. Olsalazine may also act as a free radical scavenger, and mesalazine may suppress fatty acid peroxidation.1
Target Actions Organism AHuman Cyclooxygenases inhibitorHumans AThiopurine S-methyltransferase inhibitorHumans AInterferon gamma Not Available Humans UXanthine dehydrogenase/oxidase inhibitorHumans - Absorption
After oral administration, olsalazine has limited systemic bioavailability, with less than 5% of the oral dose being absorbed.1 Based on oral and intravenous dosing studies, approximately 2.4% of a single 1 g oral dose is absorbed. Maximum serum concentrations of olsalazine appear after approximately one hour and, even after a 1 g single dose, are low (e.g., 1.6 to 6.2 µmol/L).5
Patients on daily doses of 1 g olsalazine for two to four years show a stable plasma concentration of olsalazine-S (3.3 to 12.4 µmol/L). Olsalazine-S accumulates to a steady state within two to three weeks. Serum concentrations of mesalamine are detected after four to eight hours. The peak levels of mesalamine after an oral dose of 1 g olsalazine are low (i.e., 0 to 4.3 µmol/L).5
- Volume of distribution
The steady-state volume of distribution determined in healthy volunteers is approximately 5L.1
- Protein binding
Olsalazine and its metabolite olsalazine-S, are more than 99% bound to plasma proteins. Less than 1% of both olsalazine and olsalazine-S appears undissociated in plasma. It does not interfere with the protein binding of warfarin.5
Mesalamine (5-aminosalicylic acid, 5-ASA) and its metabolite, N-acetyl-5-ASA, are 74 and 81%, respectively, bound to plasma proteins.5
- Metabolism
Olsalazine is cleaved by colonic bacteria to release its active ingredient, mesalamine. Mesalamine can undergo acetylation to form N-acetyl-5-aminosalicylic acid (N-acetyl-5-ASA, Ac-5-ASA) by the colonic epithelium; however, the extent of acetylation depends on transit time.1 Approximately 0.1% of an oral dose of olsalazine is metabolized in the liver to olsalazine-O-sulfate (olsalazine-S).5
Hover over products below to view reaction partners
- Route of elimination
Olsalazine and its metabolites are excreted in the urine.1 Total recovery of oral 14C-labeled olsalazine in animals and humans ranges from 90 to 97%. Approximately 20% of the total mesalamine is recovered in the urine. Of the total mesalamine found in the urine, more than 90% is N-acetyl-5-ASA. Only small amounts of mesalamine are detected in the urine. The remaining mesalamine is partially acetylated and excreted in the feces. From fecal dialysis, the concentration of mesalamine in the colon following olsalazine has been calculated to be 18 to 49 mmol/L.5
The urinary recovery of olsalazine is below 1%.5 Less than 5% of an oral dose (0.25 to 2g) was recovered unchanged in the feces; however, more than 50% of the oral dose was excreted in feces as unchanged olsalazine when the whole gut transit time was decreased by approximately 50%.1
- Half-life
Olsalazine has a very short serum half-life, approximately 0.9 hours. Olsalazine-S has a half-life of seven days due to slow dissociation from the protein binding site.1,5
- Clearance
Not Available
- Adverse Effects
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There is no information available regarding acute toxicity (LD50) of olsalazine. Symptoms of salicylate toxicity include nausea, vomiting and abdominal pain, tachypnea, hyperpnea, tinnitus, and neurologic symptoms (headache, dizziness, confusion, seizures). Severe intoxication may lead to electrolyte and blood pH imbalance and potentially to organ damage. There is no antidote for olsalazine overdose; however, conventional therapy for salicylate toxicity, such as gastrointestinal tract decontamination, may be beneficial in acute overdosage. Overdose should be managed with proper medical care and appropriate supportive care, including the possible use of emesis, cathartics, and activated charcoal to prevent further absorption. Fluid and electrolyte imbalance may be managed with appropriate intravenous therapy and maintenance of adequate renal function.5
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Olsalazine may decrease the excretion rate of Abacavir which could result in a higher serum level. Abciximab The risk or severity of bleeding can be increased when Olsalazine is combined with Abciximab. Acarbose Olsalazine may increase the hypoglycemic activities of Acarbose. Aceclofenac The risk or severity of nephrotoxicity can be increased when Aceclofenac is combined with Olsalazine. Acemetacin The risk or severity of nephrotoxicity can be increased when Acemetacin is combined with Olsalazine. - Food Interactions
- Take with food. Food does not affect drug absorption or exposure, but may mitigate the risk for drug-related adverse effects.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Olsalazine sodium Y7JEW0XG7I 6054-98-4 QQWFSVYVHLECFP-XBPUGJBTSA-L - Active Moieties
Name Kind UNII CAS InChI Key Mesalazine prodrug 4Q81I59GXC 89-57-6 KBOPZPXVLCULAV-UHFFFAOYSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Dipentum Capsule 250 mg/1 Oral Unither Manufacturing, LLC 1990-07-31 2010-07-31 US 
Dipentum Capsule, gelatin coated 250 mg/1 Oral Carilion Materials Management 2015-05-15 Not applicable US Dipentum Capsule, gelatin coated 250 mg/1 Oral Meda Pharmaceuticals Inc. 2015-05-15 Not applicable US Dipentum Capsule, gelatin coated 250 mg/1 Oral Carilion Materials Management 1990-07-31 Not applicable US Dipentum Capsule 250 mg Oral Atnahs Pharma Uk Limited 1995-12-31 Not applicable Canada 
Categories
- ATC Codes
- A07EC03 — Olsalazine
- Drug Categories
- Acids, Carbocyclic
- Agents causing hyperkalemia
- Agents that produce hypertension
- Alimentary Tract and Metabolism
- Aminosalicylate
- Analgesics
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antidiarrheals, Intestinal Antiinflammatory/antiinfective Agents
- Benzene Derivatives
- Benzoates
- Gastrointestinal Agents
- Hydroxy Acids
- Hydroxybenzoates
- Intestinal Antiinflammatory Agents
- Nephrotoxic agents
- Non COX-2 selective NSAIDS
- Peripheral Nervous System Agents
- Phenols
- Salicylates
- Sensory System Agents
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as azobenzenes. These are organonitrogen aromatic compounds that contain a central azo group, where each nitrogen atom is conjugated to a benzene ring.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Azobenzenes
- Sub Class
- Not Available
- Direct Parent
- Azobenzenes
- Alternative Parents
- Salicylic acids / Benzoic acids / Benzoyl derivatives / 1-hydroxy-2-unsubstituted benzenoids / Dicarboxylic acids and derivatives / Vinylogous acids / Azo compounds / Propargyl-type 1,3-dipolar organic compounds / Carboxylic acids / Organopnictogen compounds show 3 more
- Substituents
- 1-hydroxy-2-unsubstituted benzenoid / Aromatic homomonocyclic compound / Azo compound / Azobenzene / Benzenoid / Benzoic acid / Benzoic acid or derivatives / Benzoyl / Carboxylic acid / Carboxylic acid derivative show 16 more
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- ULS5I8J03O
- CAS number
- 15722-48-2
- InChI Key
- QQBDLJCYGRGAKP-FOCLMDBBSA-N
- InChI
- InChI=1S/C14H10N2O6/c17-11-3-1-7(5-9(11)13(19)20)15-16-8-2-4-12(18)10(6-8)14(21)22/h1-6,17-18H,(H,19,20)(H,21,22)/b16-15+
- IUPAC Name
- 5-[(1E)-2-(3-carboxy-4-hydroxyphenyl)diazen-1-yl]-2-hydroxybenzoic acid
- SMILES
- OC(=O)C1=CC(=CC=C1O)\N=N\C1=CC=C(O)C(=C1)C(O)=O
References
- General References
- Wadworth AN, Fitton A: Olsalazine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in inflammatory bowel disease. Drugs. 1991 Apr;41(4):647-64. doi: 10.2165/00003495-199141040-00009. [Article]
- Campbell DE, Berglindh T: Pharmacology of olsalazine. Scand J Gastroenterol Suppl. 1988;148:7-12. doi: 10.3109/00365528809101539. [Article]
- Horn H, Preclik G, Stange EF, Ditschuneit H: Modulation of arachidonic acid metabolism by olsalazine and other aminosalicylates in leukocytes. Scand J Gastroenterol. 1991 Aug;26(8):867-79. doi: 10.3109/00365529109037024. [Article]
- 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]
- FDA Approved Drug Products: DIPENTUM (olsalazine) Oral Capsules (November 2022) [Link]
- Health Canada Approved Drug Products: DIPENTUM (olsalazine sodium) Oral Capsules [Link]
- FDA Approved Drug Products: Dipentum (olsalazine) oral capsules (October 2023) [Link]
- External Links
- Human Metabolome Database
- HMDB0015380
- KEGG Drug
- D00727
- KEGG Compound
- C07323
- PubChem Compound
- 6003770
- PubChem Substance
- 46506356
- ChemSpider
- 10642377
- 32385
- ChEMBL
- CHEMBL425
- ZINC
- ZINC000003812865
- PharmGKB
- PA450700
- PDBe Ligand
- JBC
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Olsalazine
- PDB Entries
- 7era
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 Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data2 Completed Treatment Ankylosing Spondylitis (AS) 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Alaven Pharmaceutical
- Pfizer Inc.
- Pharmacia Inc.
- UCB Pharma
- Dosage Forms
Form Route Strength Capsule Oral Capsule Oral 250 mg Capsule Oral 250 mg/1 Capsule, gelatin coated Oral 250 mg/1 Tablet - Prices
Unit description Cost Unit Dipentum 250 mg capsule 1.8USD capsule DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source logP 2.3 Not Available - Predicted Properties
Property Value Source Water Solubility 0.0781 mg/mL ALOGPS logP 2.77 ALOGPS logP 4.39 Chemaxon logS -3.6 ALOGPS pKa (Strongest Acidic) 2.93 Chemaxon pKa (Strongest Basic) -0.019 Chemaxon Physiological Charge -2 Chemaxon Hydrogen Acceptor Count 8 Chemaxon Hydrogen Donor Count 4 Chemaxon Polar Surface Area 139.78 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 78.85 m3·mol-1 Chemaxon Polarizability 28.61 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.8502 Blood Brain Barrier + 0.6279 Caco-2 permeable - 0.6449 P-glycoprotein substrate Non-substrate 0.7433 P-glycoprotein inhibitor I Non-inhibitor 0.8628 P-glycoprotein inhibitor II Non-inhibitor 0.9525 Renal organic cation transporter Non-inhibitor 0.8844 CYP450 2C9 substrate Non-substrate 0.7774 CYP450 2D6 substrate Non-substrate 0.8748 CYP450 3A4 substrate Non-substrate 0.6636 CYP450 1A2 substrate Non-inhibitor 0.8006 CYP450 2C9 inhibitor Non-inhibitor 0.7804 CYP450 2D6 inhibitor Non-inhibitor 0.9047 CYP450 2C19 inhibitor Non-inhibitor 0.8638 CYP450 3A4 inhibitor Non-inhibitor 0.8309 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8912 Ames test Non AMES toxic 0.9132 Carcinogenicity Non-carcinogens 0.5546 Biodegradation Not ready biodegradable 0.8701 Rat acute toxicity 1.4882 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9506 hERG inhibition (predictor II) Non-inhibitor 0.9453
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-0udi-1941000000-280432522076c6c2ecde Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0f79-0095000000-7bb7db19b1af6177042d Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0udi-0049000000-7c76ad0d3a0538fee9aa Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-000i-0291000000-6edd53b6191e1d5f90e1 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0bt9-0191000000-3db29b271b8637083453 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-03di-0090000000-c3ec7be9279852083204 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-06tf-0190000000-17f0e51857b98451430f Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 178.3518076 predictedDarkChem Lite v0.1.0 [M-H]- 165.00941 predictedDeepCCS 1.0 (2019) [M+H]+ 175.2893076 predictedDarkChem Lite v0.1.0 [M+H]+ 167.36742 predictedDeepCCS 1.0 (2019) [M+Na]+ 175.3766076 predictedDarkChem Lite v0.1.0 [M+Na]+ 173.70184 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein group
- 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
Components:
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine (also called mercaptopurine, 6-MP or its brand name Purinethol) and 6-thioguanine (also called tioguanine or 6-TG) using S-adenosyl-L-methionine as the methyl donor (PubMed:18484748, PubMed:657528). TPMT activity modulates the cytotoxic effects of thiopurine prodrugs. A natural substrate for this enzyme has yet to be identified
- Specific Function
- S-adenosyl-l-methionine binding
- Gene Name
- TPMT
- Uniprot ID
- P51580
- Uniprot Name
- Thiopurine S-methyltransferase
- Molecular Weight
- 28180.09 Da
References
- Lewis LD, Benin A, Szumlanski CL, Otterness DM, Lennard L, Weinshilboum RM, Nierenberg DW: Olsalazine and 6-mercaptopurine-related bone marrow suppression: a possible drug-drug interaction. Clin Pharmacol Ther. 1997 Oct;62(4):464-75. [Article]
- Lennard L: TPMT in the treatment of Crohn's disease with azathioprine. Gut. 2002 Aug;51(2):143-6. [Article]
- Lennard L: Clinical implications of thiopurine methyltransferase--optimization of drug dosage and potential drug interactions. Ther Drug Monit. 1998 Oct;20(5):527-31. [Article]
- Shipkova M, Niedmann PD, Armstrong VW, Oellerich M, Wieland E: Determination of thiopurine methyltransferase activity in isolated human erythrocytes does not reflect putative in vivo enzyme inhibition by sulfasalazine. Clin Chem. 2004 Feb;50(2):438-41. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- General Function
- Type II interferon produced by immune cells such as T-cells and NK cells that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing antigen presentation (PubMed:16914093, PubMed:8666937). Primarily signals through the JAK-STAT pathway after interaction with its receptor IFNGR1 to affect gene regulation (PubMed:8349687). Upon IFNG binding, IFNGR1 intracellular domain opens out to allow association of downstream signaling components JAK2, JAK1 and STAT1, leading to STAT1 activation, nuclear translocation and transcription of IFNG-regulated genes. Many of the induced genes are transcription factors such as IRF1 that are able to further drive regulation of a next wave of transcription (PubMed:16914093). Plays a role in class I antigen presentation pathway by inducing a replacement of catalytic proteasome subunits with immunoproteasome subunits (PubMed:8666937). In turn, increases the quantity, quality, and repertoire of peptides for class I MHC loading (PubMed:8163024). Increases the efficiency of peptide generation also by inducing the expression of activator PA28 that associates with the proteasome and alters its proteolytic cleavage preference (PubMed:11112687). Up-regulates as well MHC II complexes on the cell surface by promoting expression of several key molecules such as cathepsins B/CTSB, H/CTSH, and L/CTSL (PubMed:7729559). Participates in the regulation of hematopoietic stem cells during development and under homeostatic conditions by affecting their development, quiescence, and differentiation (By similarity)
- Specific Function
- Cytokine activity
- Gene Name
- IFNG
- Uniprot ID
- P01579
- Uniprot Name
- Interferon gamma
- Molecular Weight
- 19348.165 Da
References
- Egan LJ, Sandborn WJ: Inhibition of nuclear factor kappaB by sulfasalazine: a new target for inflammatory bowel disease therapy? Gastroenterology. 1998 Nov;115(5):1295-6. [Article]
- Ito R, Shin-Ya M, Kishida T, Urano A, Takada R, Sakagami J, Imanishi J, Kita M, Ueda Y, Iwakura Y, Kataoka K, Okanoue T, Mazda O: Interferon-gamma is causatively involved in experimental inflammatory bowel disease in mice. Clin Exp Immunol. 2006 Nov;146(2):330-8. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species. Has also low oxidase activity towards aldehydes (in vitro)
- Specific Function
- 2 iron, 2 sulfur cluster binding
- Gene Name
- XDH
- Uniprot ID
- P47989
- Uniprot Name
- Xanthine dehydrogenase/oxidase
- Molecular Weight
- 146422.99 Da
References
- Campbell DE, Berglindh T: Pharmacology of olsalazine. Scand J Gastroenterol Suppl. 1988;148:7-12. doi: 10.3109/00365528809101539. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Downregulator
- Curator comments
- Olsalazine reduced the mRNA expression of this transporter in hyperuricemic mice.
- General Function
- High-capacity urate transporter, which may play a role in the urate reabsorption by proximal tubules (PubMed:18327257, PubMed:18701466, PubMed:22647630, PubMed:28083649, PubMed:36749388). May have a residual high-affinity, low-capacity glucose and fructose transporter activity (PubMed:18327257, PubMed:18701466, PubMed:18842065). Transports urate at rates 45- to 60-fold faster than glucose (PubMed:18842065). Does not transport galactose (PubMed:28083649). May mediate small uptake of adenine but not of other nucleobases (PubMed:22647630)
- Specific Function
- Carbohydrate
- Gene Name
- SLC2A9
- Uniprot ID
- Q9NRM0
- Uniprot Name
- Solute carrier family 2, facilitated glucose transporter member 9
- Molecular Weight
- 58701.205 Da
References
- Niu Y, Yang P, Li H, Li Q, Lin H, Gao L, Li L: Olsalazine Sodium Increases Renal Urate Excretion by Modulating Urate Transporters in Hyperuricemic Animals. Biol Pharm Bull. 2020 Nov 1;43(11):1653-1659. doi: 10.1248/bpb.b20-00362. Epub 2020 Aug 28. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Upregulator
- Curator comments
- Olsalazine increased the mRNA expression of this transporter in hyperuricemic mice.
- General Function
- Secondary active transporter that functions as a Na(+)-independent organic anion (OA)/dicarboxylate antiporter where the uptake of one molecule of OA into the cell is coupled with an efflux of one molecule of intracellular dicarboxylate such as 2-oxoglutarate or glutarate (PubMed:11669456, PubMed:11907186, PubMed:14675047, PubMed:22108572, PubMed:23832370, PubMed:28534121, PubMed:9950961). Mediates the uptake of OA across the basolateral side of proximal tubule epithelial cells, thereby contributing to the renal elimination of endogenous OA from the systemic circulation into the urine (PubMed:9887087). Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (PubMed:28534121). Transports prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may contribute to their renal excretion (PubMed:11907186). Also mediates the uptake of cyclic nucleotides such as cAMP and cGMP (PubMed:26377792). Involved in the transport of neuroactive tryptophan metabolites kynurenate (KYNA) and xanthurenate (XA) and may contribute to their secretion from the brain (PubMed:22108572, PubMed:23832370). May transport glutamate (PubMed:26377792). Also involved in the disposition of uremic toxins and potentially toxic xenobiotics by the renal organic anion secretory pathway, helping reduce their undesired toxicological effects on the body (PubMed:11669456, PubMed:14675047). Uremic toxins include the indoxyl sulfate (IS), hippurate/N-benzoylglycine (HA), indole acetate (IA), 3-carboxy-4- methyl-5-propyl-2-furanpropionate (CMPF) and urate (PubMed:14675047, PubMed:26377792). Xenobiotics include the mycotoxin ochratoxin (OTA) (PubMed:11669456). May also contribute to the transport of organic compounds in testes across the blood-testis-barrier (PubMed:35307651)
- Specific Function
- Alpha-ketoglutarate transmembrane transporter activity
- Gene Name
- SLC22A6
- Uniprot ID
- Q4U2R8
- Uniprot Name
- Solute carrier family 22 member 6
- Molecular Weight
- 61815.78 Da
References
- Niu Y, Yang P, Li H, Li Q, Lin H, Gao L, Li L: Olsalazine Sodium Increases Renal Urate Excretion by Modulating Urate Transporters in Hyperuricemic Animals. Biol Pharm Bull. 2020 Nov 1;43(11):1653-1659. doi: 10.1248/bpb.b20-00362. Epub 2020 Aug 28. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Upregulator
- Curator comments
- Olsalazine increased the mRNA expression of this transporter in hyperuricemic mice.
- General Function
- Functions as an organic anion/dicarboxylate exchanger that couples organic anion uptake indirectly to the sodium gradient (PubMed:14586168, PubMed:15644426, PubMed:15846473, PubMed:16455804, PubMed:31553721). Transports organic anions such as estrone 3-sulfate (E1S) and urate in exchange for dicarboxylates such as glutarate or ketoglutarate (2-oxoglutarate) (PubMed:14586168, PubMed:15846473, PubMed:15864504, PubMed:22108572, PubMed:23832370). Plays an important role in the excretion of endogenous and exogenous organic anions, especially from the kidney and the brain (PubMed:11306713, PubMed:14586168, PubMed:15846473). E1S transport is pH- and chloride-dependent and may also involve E1S/cGMP exchange (PubMed:26377792). Responsible for the transport of prostaglandin E2 (PGE2) and prostaglandin F2(alpha) (PGF2(alpha)) in the basolateral side of the renal tubule (PubMed:11907186). Involved in the transport of neuroactive tryptophan metabolites kynurenate and xanthurenate (PubMed:22108572, PubMed:23832370). Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (PubMed:28534121). May be involved in the basolateral transport of steviol, a metabolite of the popular sugar substitute stevioside (PubMed:15644426). May participate in the detoxification/ renal excretion of drugs and xenobiotics, such as the histamine H(2)-receptor antagonists fexofenadine and cimetidine, the antibiotic benzylpenicillin (PCG), the anionic herbicide 2,4-dichloro-phenoxyacetate (2,4-D), the diagnostic agent p-aminohippurate (PAH), the antiviral acyclovir (ACV), and the mycotoxin ochratoxin (OTA), by transporting these exogenous organic anions across the cell membrane in exchange for dicarboxylates such as 2-oxoglutarate (PubMed:11669456, PubMed:15846473, PubMed:16455804). Contributes to the renal uptake of potent uremic toxins (indoxyl sulfate (IS), indole acetate (IA), hippurate/N-benzoylglycine (HA) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF)), pravastatin, PCG, E1S and dehydroepiandrosterone sulfate (DHEAS), and is partly involved in the renal uptake of temocaprilat (an angiotensin-converting enzyme (ACE) inhibitor) (PubMed:14675047). May contribute to the release of cortisol in the adrenals (PubMed:15864504). Involved in one of the detoxification systems on the choroid plexus (CP), removes substrates such as E1S or taurocholate (TC), PCG, 2,4-D and PAH, from the cerebrospinal fluid (CSF) to the blood for eventual excretion in urine and bile (By similarity). Also contributes to the uptake of several other organic compounds such as the prostanoids prostaglandin E(2) and prostaglandin F(2-alpha), L-carnitine, and the therapeutic drugs allopurinol, 6-mercaptopurine (6-MP) and 5-fluorouracil (5-FU) (By similarity). Mediates the transport of PAH, PCG, and the statins pravastatin and pitavastatin, from the cerebrum into the blood circulation across the blood-brain barrier (BBB). In summary, plays a role in the efflux of drugs and xenobiotics, helping reduce their undesired toxicological effects on the body (By similarity)
- Specific Function
- Organic anion transmembrane transporter activity
- Gene Name
- SLC22A8
- Uniprot ID
- Q8TCC7
- Uniprot Name
- Organic anion transporter 3
- Molecular Weight
- 59855.585 Da
References
- Niu Y, Yang P, Li H, Li Q, Lin H, Gao L, Li L: Olsalazine Sodium Increases Renal Urate Excretion by Modulating Urate Transporters in Hyperuricemic Animals. Biol Pharm Bull. 2020 Nov 1;43(11):1653-1659. doi: 10.1248/bpb.b20-00362. Epub 2020 Aug 28. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Upregulator
- Curator comments
- Olsalazine increased the mRNA expression of this transporter in hyperuricemic mice.
- General Function
- Sodium-phosphate symporter which preferentially transports the monovalent form of phosphate with a stoichiometry of two sodium ions per phosphate ion (PubMed:11009570, PubMed:16790504, PubMed:17494632, PubMed:19726692, PubMed:7929240, PubMed:8041748). May play a role in extracellular matrix and cartilage calcification as well as in vascular calcification (PubMed:11009570). Essential for cell proliferation but this function is independent of its phosphate transporter activity (PubMed:19726692)
- Specific Function
- High-affinity phosphate
- Gene Name
- SLC20A1
- Uniprot ID
- Q8WUM9
- Uniprot Name
- Sodium-dependent phosphate transporter 1
- Molecular Weight
- 73699.01 Da
References
- Niu Y, Yang P, Li H, Li Q, Lin H, Gao L, Li L: Olsalazine Sodium Increases Renal Urate Excretion by Modulating Urate Transporters in Hyperuricemic Animals. Biol Pharm Bull. 2020 Nov 1;43(11):1653-1659. doi: 10.1248/bpb.b20-00362. Epub 2020 Aug 28. [Article]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Olsalazine and its active ingredient mesalazine inhibited ileal and colonic NA+/K+-ATPase in a concentration-dependent manner with an IC50 of 4.1 mM and 4.8 mM, respectively.
- General Function
- This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients (PubMed:29499166, PubMed:30388404). Could also be part of an osmosensory signaling pathway that senses body-fluid sodium levels and controls salt intake behavior as well as voluntary water intake to regulate sodium homeostasis (By similarity)
- Specific Function
- Atp binding
Components:
References
- Scheurlen C, Allgayer H, Kruis W, Erdmann E, Sauerbruch T: Effect of olsalazine and mesalazine on human ileal and colonic (Na+ + K+)-ATPase. A possible diarrhogenic factor? Clin Investig. 1993 Apr;71(4):286-9. doi: 10.1007/BF00184728. [Article]
- Wadworth AN, Fitton A: Olsalazine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in inflammatory bowel disease. Drugs. 1991 Apr;41(4):647-64. doi: 10.2165/00003495-199141040-00009. [Article]
Drug created at March 30, 2007 12:25 / Updated at September 18, 2024 17:45