Explore a selection of our essential drug information below, or:
Identification
- Summary
Diflunisal is an NSAID used to treat mild to moderate pain, inflammation, osteoarthritis, and rheumatoid arthritis.
- Brand Names
- Dolobid
- Generic Name
- Diflunisal
- DrugBank Accession Number
- DB00861
- Background
Diflunisal, a salicylate derivative, is a nonsteroidal anti-inflammatory agent (NSAIA) with pharmacologic actions similar to other prototypical NSAIAs. Diflunisal possesses anti-inflammatory, analgesic and antipyretic activity. Though its mechanism of action has not been clearly established, most of its actions appear to be associated with inhibition of prostaglandin synthesis via the arachidonic acid pathway. Diflunisal is used to relieve pain accompanied with inflammation and in the symptomatic treatment of rheumatoid arthritis and osteoarthritis.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Diflunisal (DB00861)
- Weight
- Average: 250.1976
Monoisotopic: 250.044150532 - Chemical Formula
- C13H8F2O3
- Synonyms
- 2-(hydroxy)-5-(2,4-difluorophenyl)benzoic acid
- 2',4'-difluoro-4-hydroxy-3-biphenylcarboxylic acid
- 5-(2,4-difluorophenyl)salicylic acid
- Diflunisal
- Diflunisalum
- External IDs
- MK 647
Pharmacology
- Indication
For symptomatic treatment of mild to moderate pain accompanied by inflammation (e.g. musculoskeletal trauma, post-dental extraction, post-episiotomy), osteoarthritis, and rheumatoid arthritis.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Symptomatic treatment of Osteoarthritis •••••••••••• Symptomatic treatment of Rheumatoid arthritis •••••••••••• Symptomatic treatment of Mild pain •••••••••••• Symptomatic treatment of Moderate pain •••••••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Diflunisal is a nonsteroidal drug with analgesic, anti-inflammatory and antipyretic properties. It is a peripherally-acting non-narcotic analgesic drug. Habituation, tolerance and addiction have not been reported. Diflunisal is a difluorophenyl derivative of salicylic acid. Chemically, diflunisal differs from aspirin (acetylsalicylic acid) in two respects. The first of these two is the presence of a difluorophenyl substituent at carbon 1. The second difference is the removal of the 0-acetyl group from the carbon 4 position. Diflunisal is not metabolized to salicylic acid, and the fluorine atoms are not displaced from the difluorophenyl ring structure.
- Mechanism of action
The precise mechanism of the analgesic and anti-inflammatory actions of diflunisal is not known. Diflunisal is a prostaglandin synthetase inhibitor. In animals, prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain. Since prostaglandins are known to be among the mediators of pain and inflammation, the mode of action of diflunisal may be due to a decrease of prostaglandins in peripheral tissues.
Target Actions Organism AProstaglandin G/H synthase 2 inhibitorHumans UProstaglandin G/H synthase 1 inhibitorHumans - Absorption
Rapidly and completely absorbed following oral administration, with a bioavailability of 80-90%. Peak plasma concentrations are achieved 2 - 3 hours following oral administration.
- Volume of distribution
Not Available
- Protein binding
At least 98 to 99% of diflunisal in plasma is bound to proteins.
- Metabolism
Hepatic, primarily via glucuronide conjugation (90% of administered dose).
- Route of elimination
The drug is excreted in the urine as two soluble glucuronide conjugates accounting for about 90% of the administered dose. Little or no diflunisal is excreted in the feces.
- Half-life
8 to 12 hours
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Oral LD50 in rat, mouse, and rabbit is 392 mg/kg, 439 mg/kg, and 603 mg/kg, respectively. Symptoms of overdose include drowsiness, nausea, vomiting, diarrhea, hyperventilation, tachycardia, sweating, tinnitus, disorientation, stupor, and coma. As a monotherapy, the smallest dosage capable of causing death was reported as 15 grams.
Selective COX-2 inhibitors have been associated with increased risk of serious cardiovascular events (e.g. myocardial infarction, stroke) in some patients. Current data is insufficient to assess the cardiovascular risk of diflunisal. Short-term use does not appear to be associated with increased cardiovascular risk (except when used immediately following coronary artery bypass graft (CABG) surgery). Risk of GI toxicity including bleeding, ulceration and perforation. Risk of direct renal injury, including renal papillary necrosis. Severe hepatic reactions, including cholestasis and/or jaundice, have been reported. May cause rash or hypersensitivity syndrome.
- Pathways
Pathway Category Diflunisal Action Pathway Drug action - 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 Diflunisal may decrease the excretion rate of Abacavir which could result in a higher serum level. Abciximab The risk or severity of bleeding and hemorrhage can be increased when Diflunisal is combined with Abciximab. Acamprosate The excretion of Acamprosate can be decreased when combined with Diflunisal. Acarbose Diflunisal may increase the hypoglycemic activities of Acarbose. Acebutolol Diflunisal may decrease the antihypertensive activities of Acebutolol. - Food Interactions
- Avoid alcohol.
- Take with food. Food reduces irritation.
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 Images
- International/Other Brands
- Anton (Everest) / Dolobid (Merck)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Diflunisal Tablet 250 mg Oral Aa Pharma Inc 1993-12-31 Not applicable Canada 
Diflunisal Tablet 500 mg Oral Aa Pharma Inc 1993-12-31 Not applicable Canada Diflunisal-250 - Tab 250mg Tablet 250 mg / tab Oral Pro Doc Limitee 1995-12-31 2000-07-31 Canada Diflunisal-500 - Tab 500mg Tablet 500 mg / tab Oral Pro Doc Limitee 1995-12-31 2000-07-31 Canada Dolobid Tab 250mg Tablet 250 mg / tab Oral Merck Frosst Canada & Cie, Merck Frosst Canada & Co. 1983-12-31 1998-08-14 Canada - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Diflunisal Tablet, film coated 500 mg/1 Oral Teva Pharmaceuticals USA, Inc. 2021-06-30 Not applicable US 
Diflunisal Tablet, film coated 500 mg/1 Oral Rising Pharmaceuticals 2012-05-01 Not applicable US Diflunisal Tablet, film coated 250 mg/1 Oral Heritage Pharmaceuticals Inc. d/b/a Avet Pharmaceuticals Inc. 2024-08-16 2024-08-16 US Diflunisal Tablet, film coated 500 mg/1 Oral Chartwell Rx, Llc 2012-03-08 Not applicable US Diflunisal Tablet, film coated 500 mg/1 Oral PD-Rx Pharmaceuticals, Inc. 1992-11-01 2019-09-12 US
Categories
- ATC Codes
- N02BA11 — Diflunisal
- Drug Categories
- Agents causing hyperkalemia
- Agents that produce hypertension
- Analgesics
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Anti-Inflammatory Agents, Non-Steroidal (Non-Selective)
- Antirheumatic Agents
- Benzene Derivatives
- Cyclooxygenase Inhibitors
- Drugs causing inadvertant photosensitivity
- Drugs that are Mainly Renally Excreted
- Enzyme Inhibitors
- Hydroxybenzoates
- Nephrotoxic agents
- Nervous System
- Non COX-2 selective NSAIDS
- OAT1/SLC22A6 inhibitors
- Other Nonsteroidal Anti-inflammatory Agents
- Peripheral Nervous System Agents
- Phenols
- Photosensitizing Agents
- Salicylates
- Salicylic Acid and Derivatives
- Sensory System Agents
- UGT1A9 Inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as biphenyls and derivatives. These are organic compounds containing to benzene rings linked together by a C-C bond.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Biphenyls and derivatives
- Direct Parent
- Biphenyls and derivatives
- Alternative Parents
- Salicylic acids / Benzoic acids / Benzoyl derivatives / Fluorobenzenes / 1-hydroxy-2-unsubstituted benzenoids / Aryl fluorides / Vinylogous acids / Monocarboxylic acids and derivatives / Carboxylic acids / Organooxygen compounds show 3 more
- Substituents
- 1-hydroxy-2-unsubstituted benzenoid / Aromatic homomonocyclic compound / Aryl fluoride / Aryl halide / Benzoic acid / Benzoic acid or derivatives / Benzoyl / Biphenyl / Carboxylic acid / Carboxylic acid derivative show 14 more
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- organofluorine compound, monohydroxybenzoic acid (CHEBI:39669)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 7C546U4DEN
- CAS number
- 22494-42-4
- InChI Key
- HUPFGZXOMWLGNK-UHFFFAOYSA-N
- InChI
- InChI=1S/C13H8F2O3/c14-8-2-3-9(11(15)6-8)7-1-4-12(16)10(5-7)13(17)18/h1-6,16H,(H,17,18)
- IUPAC Name
- 2',4'-difluoro-4-hydroxy-[1,1'-biphenyl]-3-carboxylic acid
- SMILES
- OC(=O)C1=C(O)C=CC(=C1)C1=C(F)C=C(F)C=C1
References
- Synthesis Reference
Ruyle, W.V., Jarett, L.H. and Matzuk, A.R. ; U S . Patent 3,714,226; January 30, 1973; assigned to Merck & Co., Inc.
- General References
- Not Available
- External Links
- Human Metabolome Database
- HMDB0014999
- KEGG Drug
- D00130
- KEGG Compound
- C01691
- PubChem Compound
- 3059
- PubChem Substance
- 46507807
- ChemSpider
- 2951
- BindingDB
- 50240510
- 3393
- ChEBI
- 39669
- ChEMBL
- CHEMBL898
- ZINC
- ZINC000000020243
- Therapeutic Targets Database
- DAP000152
- PharmGKB
- PA449313
- PDBe Ligand
- 1FL
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- PDRhealth
- PDRhealth Drug Page
- Wikipedia
- Diflunisal
- PDB Entries
- 2bxe / 3d2t / 4i89 / 5g48 / 6e70 / 6e73 / 6e78 / 7k12 / 7ycq
- FDA label
- Download (94.1 KB)
- MSDS
- Download (73.4 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 Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Completed Not Available Amyloidosis 1 somestatus stop reason just information to hide 4 Terminated Treatment Human Immunodeficiency Virus (HIV) Infections 1 somestatus stop reason just information to hide 2 Completed Treatment Type 2 Diabetes Mellitus 1 somestatus stop reason just information to hide 2, 3 Completed Treatment Amyloidosis, Familial / Familial Amyloid Polyneuropathy (FAP) 1 somestatus stop reason just information to hide 1 Completed Diagnostic Healthy Volunteers (HV) 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Purepac pharmaceutical co
- Roxane laboratories inc
- Sandoz inc
- Teva pharmaceuticals usa inc
- Watson laboratories inc
- Merck and co inc
- Packagers
- A-S Medication Solutions LLC
- Dispensing Solutions
- Diversified Healthcare Services Inc.
- Endo Pharmaceuticals Inc.
- H.J. Harkins Co. Inc.
- Lake Erie Medical and Surgical Supply
- Major Pharmaceuticals
- Murfreesboro Pharmaceutical Nursing Supply
- Nucare Pharmaceuticals Inc.
- PD-Rx Pharmaceuticals Inc.
- Pharmedix
- Physicians Total Care Inc.
- Preferred Pharmaceuticals Inc.
- Professional Co.
- Redpharm Drug
- Shanghai Multi Med Union Co. Ltd.
- Southwood Pharmaceuticals
- St Mary's Medical Park Pharmacy
- Stat Rx Usa
- Teva Pharmaceutical Industries Ltd.
- Dosage Forms
Form Route Strength Capsule Tablet Oral 250 mg Tablet Oral 500 mg Tablet Oral 500 mg/1 Tablet, film coated Oral 500 mg/1 Tablet Oral 250 mg / tab Tablet Oral 500 mg / tab Tablet Oral Tablet, film coated Oral 250 mg/1 Tablet, film coated Oral 375 mg/1 Tablet, film coated Oral Tablet, film coated Oral 500 mg Pill Tablet, coated Oral 250 mg - Prices
Unit description Cost Unit Dolobid 60 500 mg tablet Bottle 92.83USD bottle Diflunisal 250 mg tablet 1.74USD tablet Diflunisal powder 1.56USD g Diflunisal 500 mg tablet 1.46USD tablet Apo-Diflunisal 500 mg Tablet 0.75USD tablet 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 melting point (°C) 210-211 Ruyle, W.V., Jarett, L.H. and Matzuk, A.R. ; U S . Patent 3,714,226; January 30, 1973; assigned to Merck & Co., Inc. water solubility Practically insoluble (14.5 mg/L) at neutral or acidic pH. Not Available logP 4.44 SANGSTER (1993) - Predicted Properties
Property Value Source Water Solubility 0.0711 mg/mL ALOGPS logP 3.11 ALOGPS logP 3.91 Chemaxon logS -3.6 ALOGPS pKa (Strongest Acidic) 2.69 Chemaxon pKa (Strongest Basic) -6.3 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 57.53 Å2 Chemaxon Rotatable Bond Count 2 Chemaxon Refractivity 60.86 m3·mol-1 Chemaxon Polarizability 22.29 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 + 0.9945 Blood Brain Barrier + 0.8047 Caco-2 permeable + 0.8866 P-glycoprotein substrate Non-substrate 0.6927 P-glycoprotein inhibitor I Non-inhibitor 0.9407 P-glycoprotein inhibitor II Non-inhibitor 0.9735 Renal organic cation transporter Non-inhibitor 0.911 CYP450 2C9 substrate Non-substrate 0.7982 CYP450 2D6 substrate Non-substrate 0.9201 CYP450 3A4 substrate Non-substrate 0.7145 CYP450 1A2 substrate Non-inhibitor 0.9046 CYP450 2C9 inhibitor Inhibitor 0.6684 CYP450 2D6 inhibitor Non-inhibitor 0.9357 CYP450 2C19 inhibitor Non-inhibitor 0.9025 CYP450 3A4 inhibitor Non-inhibitor 0.8309 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.5156 Ames test Non AMES toxic 0.9666 Carcinogenicity Non-carcinogens 0.7828 Biodegradation Not ready biodegradable 0.988 Rat acute toxicity 2.7735 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.983 hERG inhibition (predictor II) Non-inhibitor 0.9178
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 157.1599902 predictedDarkChem Lite v0.1.0 [M-H]- 161.43367 predictedDeepCCS 1.0 (2019) [M+H]+ 157.9597902 predictedDarkChem Lite v0.1.0 [M+H]+ 163.81215 predictedDeepCCS 1.0 (2019) [M+Na]+ 157.1048902 predictedDarkChem Lite v0.1.0 [M+Na]+ 169.88481 predictedDeepCCS 1.0 (2019)
Targets
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
- 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
- Cappon GD, Cook JC, Hurtt ME: Relationship between cyclooxygenase 1 and 2 selective inhibitors and fetal development when administered to rats and rabbits during the sensitive periods for heart development and midline closure. Birth Defects Res B Dev Reprod Toxicol. 2003 Feb;68(1):47-56. [Article]
- Jeske AH: COX-2 inhibitors and dental pain control. J Gt Houst Dent Soc. 1999 Nov;71(4):39-40. [Article]
- Mao H, Hajduk PJ, Craig R, Bell R, Borre T, Fesik SW: Rational design of diflunisal analogues with reduced affinity for human serum albumin. J Am Chem Soc. 2001 Oct 31;123(43):10429-35. [Article]
- Moore PA, Hersh EV: Celecoxib and rofecoxib. The role of COX-2 inhibitors in dental practice. J Am Dent Assoc. 2001 Apr;132(4):451-6. [Article]
- Young JM, Panah S, Satchawatcharaphong C, Cheung PS: Human whole blood assays for inhibition of prostaglandin G/H synthases-1 and -2 using A23187 and lipopolysaccharide stimulation of thromboxane B2 production. Inflamm Res. 1996 May;45(5):246-53. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- 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
- Unknown
- 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
- Cappon GD, Cook JC, Hurtt ME: Relationship between cyclooxygenase 1 and 2 selective inhibitors and fetal development when administered to rats and rabbits during the sensitive periods for heart development and midline closure. Birth Defects Res B Dev Reprod Toxicol. 2003 Feb;68(1):47-56. [Article]
- Chen QH, Rao PN, Knaus EE: Design, synthesis, and biological evaluation of N-acetyl-2-carboxybenzenesulfonamides: a novel class of cyclooxygenase-2 (COX-2) inhibitors. Bioorg Med Chem. 2005 Apr 1;13(7):2459-68. [Article]
- Young JM, Panah S, Satchawatcharaphong C, Cheung PS: Human whole blood assays for inhibition of prostaglandin G/H synthases-1 and -2 using A23187 and lipopolysaccharide stimulation of thromboxane B2 production. Inflamm Res. 1996 May;45(5):246-53. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:15472229, PubMed:16595710, PubMed:18004212, PubMed:18052087, PubMed:18674515, PubMed:18719240, PubMed:19545173, PubMed:23288867). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:15472229, PubMed:16595710, PubMed:23288867). Catalyzes the glucuronidation of endogenous steroid hormones such as androgens and estrogens (PubMed:15472229, PubMed:16595710, PubMed:18719240, PubMed:23288867). Produces dihydrotestosterone (DHT) diglucuronide from the DHT after two subsequent glucoronidation steps (PubMed:16595710). Also catalyzes the glucuronidation of the isoflavones genistein, daidzein, glycitein, formononetin, biochanin A and prunetin, which are phytoestrogens with anticancer and cardiovascular properties (PubMed:18052087, PubMed:19545173). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist caderastan, a drug which can inhibit the effect of angiotensin II (PubMed:18674515). Also metabolizes mycophenolate, an immunosuppressive agent (PubMed:15470161, PubMed:18004212)
- Specific Function
- enzyme binding
- Gene Name
- UGT1A8
- Uniprot ID
- Q9HAW9
- Uniprot Name
- UDP-glucuronosyltransferase 1A8
- Molecular Weight
- 59741.035 Da
References
- Cheng Z, Radominska-Pandya A, Tephly TR: Studies on the substrate specificity of human intestinal UDP- lucuronosyltransferases 1A8 and 1A10. Drug Metab Dispos. 1999 Oct;27(10):1165-70. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:12181437, PubMed:15470161, PubMed:15472229, PubMed:18004212, PubMed:18052087, PubMed:18674515, PubMed:19545173). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:12181437, PubMed:18004212). Catalyzes the glucuronidation of endogenous estrogen hormones such as estradiol and estrone (PubMed:15472229). Also catalyzes the glucuronidation of the isoflavones genistein, daidzein, glycitein, formononetin, biochanin A and prunetin, which are phytoestrogens with anticancer and cardiovascular properties (PubMed:18052087, PubMed:19545173). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist caderastan, a drug which can inhibit the effect of angiotensin II (PubMed:18674515). Involved in the biotransformation of 7-ethyl-10-hydroxycamptothecin (SN-38), the pharmacologically active metabolite of the anticancer drug irinotecan (PubMed:12181437, PubMed:20610558). Also metabolizes mycophenolate, an immunosuppressive agent (PubMed:15470161, PubMed:18004212)
- Specific Function
- enzyme binding
- Gene Name
- UGT1A9
- Uniprot ID
- O60656
- Uniprot Name
- UDP-glucuronosyltransferase 1A9
- Molecular Weight
- 59940.495 Da
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain
- Specific Function
- hormone activity
- Gene Name
- TTR
- Uniprot ID
- P02766
- Uniprot Name
- Transthyretin
- Molecular Weight
- 15886.88 Da
References
- Adamski-Werner SL, Palaninathan SK, Sacchettini JC, Kelly JW: Diflunisal analogues stabilize the native state of transthyretin. Potent inhibition of amyloidogenesis. J Med Chem. 2004 Jan 15;47(2):355-74. [Article]
- Almeida MR, Macedo B, Cardoso I, Alves I, Valencia G, Arsequell G, Planas A, Saraiva MJ: Selective binding to transthyretin and tetramer stabilization in serum from patients with familial amyloidotic polyneuropathy by an iodinated diflunisal derivative. Biochem J. 2004 Jul 15;381(Pt 2):351-6. [Article]
- Gales L, Macedo-Ribeiro S, Arsequell G, Valencia G, Saraiva MJ, Damas AM: Human transthyretin in complex with iododiflunisal: structural features associated with a potent amyloid inhibitor. Biochem J. 2005 Jun 1;388(Pt 2):615-21. [Article]
- Miller SR, Sekijima Y, Kelly JW: Native state stabilization by NSAIDs inhibits transthyretin amyloidogenesis from the most common familial disease variants. Lab Invest. 2004 May;84(5):545-52. [Article]
- Tojo K, Sekijima Y, Kelly JW, Ikeda S: Diflunisal stabilizes familial amyloid polyneuropathy-associated transthyretin variant tetramers in serum against dissociation required for amyloidogenesis. Neurosci Res. 2006 Dec;56(4):441-9. Epub 2006 Oct 6. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (PubMed:19021548). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (PubMed:6234017). Does not prevent iron uptake by the bacterial siderophore aerobactin (PubMed:6234017)
- Specific Function
- antioxidant activity
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Albumin
- Molecular Weight
- 69365.94 Da
References
- Davilas A, Koupparis M, Macheras P, Valsami G: In-vitro study on the competitive binding of diflunisal and uraemic toxins to serum albumin and human plasma using a potentiometric ion-probe technique. J Pharm Pharmacol. 2006 Nov;58(11):1467-74. [Article]
- Mao H, Hajduk PJ, Craig R, Bell R, Borre T, Fesik SW: Rational design of diflunisal analogues with reduced affinity for human serum albumin. J Am Chem Soc. 2001 Oct 31;123(43):10429-35. [Article]
- Rehse K, Fiedler B: [Determination of the protein binding of drugs by continuous ultrafiltration. 9. Comparison of the binding of nonsteroid antirheumatics to human serum albumin and their interaction with phenprocoumon]. Arch Pharm (Weinheim). 1989 Apr;322(4):241-3. [Article]
- Verbeeck RK, De Schepper PJ: Influence of chronic renal failure and hemodialysis on diflunisal plasma protein binding. Clin Pharmacol Ther. 1980 May;27(5):628-35. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- 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
- Mulato AS, Ho ES, Cihlar T: Nonsteroidal anti-inflammatory drugs efficiently reduce the transport and cytotoxicity of adefovir mediated by the human renal organic anion transporter 1. J Pharmacol Exp Ther. 2000 Oct;295(1):10-5. [Article]
- Apiwattanakul N, Sekine T, Chairoungdua A, Kanai Y, Nakajima N, Sophasan S, Endou H: Transport properties of nonsteroidal anti-inflammatory drugs by organic anion transporter 1 expressed in Xenopus laevis oocytes. Mol Pharmacol. 1999 May;55(5):847-54. [Article]
Drug created at June 13, 2005 13:24 / Updated at October 06, 2024 08:03