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Identification
NameDiflunisal
Accession NumberDB00861  (APRD00922, DB06895)
TypeSmall Molecule
GroupsApproved
Description

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.

Structure
Thumb
Synonyms
2-(Hydroxy)-5-(2,4-difluorophenyl)benzoic acid
2',4'-Difluoro-4-hydroxy-3-biphenylcarboxylic acid
5-(2,4-Difluorophenyl)salicylic acid
Diflunisal
Diflunisal
Diflunisal
Diflunisalum
Dolobid
External Identifiers
  • MK 647
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Diflunisaltablet500 mgoralAa Pharma Inc1993-12-31Not applicableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Diflunisaltablet250 mgoralAa Pharma Inc1993-12-31Not applicableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Diflunisal-250 - Tab 250mgtablet250 mgoralPro Doc Limitee1995-12-312000-07-31Canada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Diflunisal-500 - Tab 500mgtablet500 mgoralPro Doc Limitee1995-12-312000-07-31Canada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Dolobid Tab 250mgtablet250 mgoralMerck Frosst Canada & Cie, Merck Frosst Canada & Co.1983-12-311998-08-14Canada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Dolobid Tab 500mgtablet500 mgoralMerck Frosst Canada & Cie, Merck Frosst Canada & Co.1983-12-312000-08-03Canada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Novo-diflunisaltablet500 mgoralTeva Canada Limited1993-12-31Not applicableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Novo-diflunisaltablet250 mgoralTeva Canada Limited1993-12-31Not applicableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Nu-diflunisal Tab 250mgtablet250 mgoralNu Pharm Inc1994-12-312012-09-04Canada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Nu-diflunisal Tab 500mgtablet500 mgoralNu Pharm Inc1994-12-312012-09-04Canada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Diflunisaltablet, film coated500 mg/1oralTeva Pharmaceuticals USA Inc1992-11-01Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Diflunisaltablet, film coated500 mg/1oralCarilion Materials Management1992-11-01Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Diflunisaltablet, film coated500 mg/1oralRising Pharmaceuticals Inc.2012-05-01Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Diflunisaltablet, film coated500 mg/1oralPd Rx Pharmaceuticals, Inc.2010-08-20Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Diflunisaltablet, film coated500 mg/1oralPhysicians Total Care, Inc.2009-07-21Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Diflunisaltablet, film coated500 mg/1oralA S Medication Solutions Llc1992-11-01Not applicableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Over the Counter ProductsNot Available
International Brands
NameCompany
AntonEverest
DolobidMerck
Brand mixturesNot Available
SaltsNot Available
Categories
CAS number22494-42-4
WeightAverage: 250.1976
Monoisotopic: 250.044150532
Chemical FormulaC13H8F2O3
InChI KeyInChIKey=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
5-(2,4-difluorophenyl)-2-hydroxybenzoic acid
SMILES
OC(=O)C1=C(O)C=CC(=C1)C1=C(F)C=C(F)C=C1
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBiphenyls and derivatives
Direct ParentBiphenyls and derivatives
Alternative Parents
Substituents
  • Biphenyl
  • Salicylic acid
  • Salicylic acid or derivatives
  • Hydroxybenzoic acid
  • Benzoic acid
  • Benzoic acid or derivatives
  • Benzoyl
  • Phenol
  • Halobenzene
  • Fluorobenzene
  • Aryl halide
  • Aryl fluoride
  • Vinylogous acid
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organofluoride
  • Organohalogen compound
  • Carbonyl group
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Pharmacology
IndicationFor symptomatic treatment of mild to moderate pain accompanied by inflammation (e.g. musculoskeletal trauma, post-dental extraction, post-episiotomy), osteoarthritis, and rheumatoid arthritis.
PharmacodynamicsDiflunisal 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 actionThe 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.
AbsorptionRapidly 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 distributionNot Available
Protein bindingAt least 98 to 99% of diflunisal in plasma is bound to proteins.
Metabolism

Hepatic, primarily via glucuronide conjugation (90% of administered dose).

Route of eliminationThe 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 life8 to 12 hours
ClearanceNot Available
ToxicityOral 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. The lowest dose without the presence of other medicines which caused death was 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.

Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9945
Blood Brain Barrier+0.8047
Caco-2 permeable+0.8866
P-glycoprotein substrateNon-substrate0.6927
P-glycoprotein inhibitor INon-inhibitor0.9407
P-glycoprotein inhibitor IINon-inhibitor0.9735
Renal organic cation transporterNon-inhibitor0.911
CYP450 2C9 substrateNon-substrate0.7982
CYP450 2D6 substrateNon-substrate0.9201
CYP450 3A4 substrateNon-substrate0.7145
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorInhibitor0.6684
CYP450 2D6 inhibitorNon-inhibitor0.9357
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5156
Ames testNon AMES toxic0.9666
CarcinogenicityNon-carcinogens0.7828
BiodegradationNot ready biodegradable0.988
Rat acute toxicity2.7735 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.983
hERG inhibition (predictor II)Non-inhibitor0.9178
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Purepac pharmaceutical co
  • Roxane laboratories inc
  • Sandoz inc
  • Teva pharmaceuticals usa inc
  • Watson laboratories inc
  • Merck and co inc
Packagers
Dosage forms
FormRouteStrength
Tabletoral250 mg
Tabletoral500 mg
Tablet, film coatedoral500 mg/1
Prices
Unit descriptionCostUnit
Dolobid 60 500 mg tablet Bottle92.83USD bottle
Diflunisal 250 mg tablet1.74USD tablet
Diflunisal powder1.56USD g
Diflunisal 500 mg tablet1.46USD tablet
Apo-Diflunisal 500 mg Tablet0.75USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point210-211Ruyle, W.V., Jarett, L.H. and Matzuk, A.R. ; U S . Patent 3,714,226; January 30, 1973; assigned to Merck & Co., Inc.
water solubilityPractically insoluble (14.5 mg/L) at neutral or acidic pH.Not Available
logP4.44SANGSTER (1993)
Predicted Properties
PropertyValueSource
Water Solubility0.0711 mg/mLALOGPS
logP3.11ALOGPS
logP3.91ChemAxon
logS-3.5ALOGPS
pKa (Strongest Acidic)2.69ChemAxon
pKa (Strongest Basic)-6.3ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area57.53 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity60.86 m3·mol-1ChemAxon
Polarizability22.29 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
MSMass Spectrum (Electron Ionization)splash10-4qz0000000-d231ff5a9ac7d9769d2dView in MoNA
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 ReferencesNot Available
External Links
ATC CodesN02BA11
AHFS Codes
  • 28:08.04.92
PDB EntriesNot Available
FDA labelDownload (94.1 KB)
MSDSDownload (73.4 KB)
Interactions
Drug Interactions
Drug
AbciximabDiflunisal may increase the anticoagulant activities of Abciximab.
AcenocoumarolDiflunisal may increase the anticoagulant activities of Acenocoumarol.
Acetylsalicylic acidThe risk or severity of adverse effects can be increased when Diflunisal is combined with Acetylsalicylic acid.
AliskirenDiflunisal may decrease the antihypertensive activities of Aliskiren.
AlteplaseDiflunisal may increase the anticoagulant activities of Alteplase.
AmikacinDiflunisal may decrease the excretion rate of Amikacin which could result in a lower serum level and potentially a reduction in efficacy.
AmitriptylineAmitriptyline may increase the antiplatelet activities of Diflunisal.
AnistreplaseDiflunisal may increase the anticoagulant activities of Anistreplase.
ApixabanThe risk or severity of adverse effects can be increased when Diflunisal is combined with Apixaban.
ArbekacinDiflunisal may decrease the excretion rate of Arbekacin which could result in a lower serum level and potentially a reduction in efficacy.
BalsalazideDiflunisal may increase the nephrotoxic activities of Balsalazide.
Citric AcidDiflunisal may increase the anticoagulant activities of Citric Acid.
ColesevelamColesevelam can cause a decrease in the absorption of Diflunisal resulting in a reduced serum concentration and potentially a decrease in efficacy.
CollagenaseThe risk or severity of adverse effects can be increased when Diflunisal is combined with Collagenase.
CyclosporineDiflunisal may increase the nephrotoxic activities of Cyclosporine.
Dabigatran etexilateDiflunisal may increase the anticoagulant activities of Dabigatran etexilate.
DalteparinDiflunisal may increase the anticoagulant activities of Dalteparin.
DasatinibDasatinib may increase the anticoagulant activities of Diflunisal.
DeferasiroxThe risk or severity of adverse effects can be increased when Diflunisal is combined with Deferasirox.
Deoxycholic AcidThe risk or severity of adverse effects can be increased when Diflunisal is combined with Deoxycholic Acid.
DesmopressinThe risk or severity of adverse effects can be increased when Diflunisal is combined with Desmopressin.
DexketoprofenThe risk or severity of adverse effects can be increased when Dexketoprofen is combined with Diflunisal.
DiclofenacThe risk or severity of adverse effects can be increased when Diclofenac is combined with Diflunisal.
DicoumarolDiflunisal may increase the anticoagulant activities of Dicoumarol.
DigoxinThe serum concentration of Digoxin can be increased when it is combined with Diflunisal.
DrospirenoneDiflunisal may increase the hyperkalemic activities of Drospirenone.
Edetic AcidDiflunisal may increase the anticoagulant activities of Edetic Acid.
EnoxaparinDiflunisal may increase the anticoagulant activities of Enoxaparin.
EplerenoneDiflunisal may decrease the antihypertensive activities of Eplerenone.
Ethyl biscoumacetateDiflunisal may increase the anticoagulant activities of Ethyl biscoumacetate.
FloctafenineThe risk or severity of adverse effects can be increased when Floctafenine is combined with Diflunisal.
FludrocortisoneThe risk or severity of adverse effects can be increased when Fludrocortisone is combined with Diflunisal.
Fondaparinux sodiumDiflunisal may increase the anticoagulant activities of Fondaparinux sodium.
FramycetinDiflunisal may decrease the excretion rate of Framycetin which could result in a lower serum level and potentially a reduction in efficacy.
GentamicinDiflunisal may decrease the excretion rate of Gentamicin which could result in a lower serum level and potentially a reduction in efficacy.
GlucosamineGlucosamine may increase the antiplatelet activities of Diflunisal.
HaloperidolThe risk or severity of adverse effects can be increased when Diflunisal is combined with Haloperidol.
HeparinDiflunisal may increase the anticoagulant activities of Heparin.
HomoharringtonineThe risk or severity of adverse effects can be increased when Diflunisal is combined with Homoharringtonine.
HydralazineDiflunisal may decrease the antihypertensive activities of Hydralazine.
IbritumomabThe risk or severity of adverse effects can be increased when Diflunisal is combined with Ibritumomab.
IbrutinibThe risk or severity of adverse effects can be increased when Ibrutinib is combined with Diflunisal.
IcosapentThe risk or severity of adverse effects can be increased when Diflunisal is combined with Icosapent.
InfliximabThe risk or severity of adverse effects can be increased when Infliximab is combined with Diflunisal.
KanamycinDiflunisal may decrease the excretion rate of Kanamycin which could result in a lower serum level and potentially a reduction in efficacy.
KetorolacThe risk or severity of adverse effects can be increased when Ketorolac is combined with Diflunisal.
LimaprostLimaprost may increase the antiplatelet activities of Diflunisal.
LithiumThe serum concentration of Lithium can be increased when it is combined with Diflunisal.
MethotrexateThe serum concentration of Methotrexate can be increased when it is combined with Diflunisal.
MorniflumateThe risk or severity of adverse effects can be increased when Morniflumate is combined with Diflunisal.
NadololDiflunisal may decrease the antihypertensive activities of Nadolol.
NeomycinDiflunisal may decrease the excretion rate of Neomycin which could result in a lower serum level and potentially a reduction in efficacy.
NetilmicinDiflunisal may decrease the excretion rate of Netilmicin which could result in a lower serum level and potentially a reduction in efficacy.
ObinutuzumabThe risk or severity of adverse effects can be increased when Diflunisal is combined with Obinutuzumab.
Omega-3 fatty acidsOmega-3 fatty acids may increase the antiplatelet activities of Diflunisal.
PamidronateThe risk or severity of adverse effects can be increased when Diflunisal is combined with Pamidronate.
ParoxetineParoxetine may increase the antiplatelet activities of Diflunisal.
PemetrexedThe serum concentration of Pemetrexed can be increased when it is combined with Diflunisal.
Pentosan PolysulfateThe risk or severity of adverse effects can be increased when Pentosan Polysulfate is combined with Diflunisal.
PentoxifyllinePentoxifylline may increase the antiplatelet activities of Diflunisal.
PerindoprilThe risk or severity of adverse effects can be increased when Perindopril is combined with Diflunisal.
PhenindioneDiflunisal may increase the anticoagulant activities of Phenindione.
PhenprocoumonDiflunisal may increase the anticoagulant activities of Phenprocoumon.
PorfimerDiflunisal may increase the photosensitizing activities of Porfimer.
PralatrexateThe serum concentration of Pralatrexate can be increased when it is combined with Diflunisal.
ProbenecidThe serum concentration of Diflunisal can be increased when it is combined with Probenecid.
ReteplaseDiflunisal may increase the anticoagulant activities of Reteplase.
RibostamycinDiflunisal may decrease the excretion rate of Ribostamycin which could result in a lower serum level and potentially a reduction in efficacy.
RidogrelDiflunisal may increase the anticoagulant activities of Ridogrel.
RivaroxabanDiflunisal may increase the anticoagulant activities of Rivaroxaban.
Salicylate-sodiumThe risk or severity of adverse effects can be increased when Diflunisal is combined with Salicylate-sodium.
SparfloxacinDiflunisal may increase the neuroexcitatory activities of Sparfloxacin.
SpectinomycinDiflunisal may decrease the excretion rate of Spectinomycin which could result in a lower serum level and potentially a reduction in efficacy.
StreptokinaseDiflunisal may increase the anticoagulant activities of Streptokinase.
StreptomycinDiflunisal may decrease the excretion rate of Streptomycin which could result in a lower serum level and potentially a reduction in efficacy.
SulodexideDiflunisal may increase the anticoagulant activities of Sulodexide.
TacrolimusDiflunisal may increase the nephrotoxic activities of Tacrolimus.
TalniflumateThe risk or severity of adverse effects can be increased when Talniflumate is combined with Diflunisal.
TenecteplaseDiflunisal may increase the anticoagulant activities of Tenecteplase.
TenofovirThe risk or severity of adverse effects can be increased when Diflunisal is combined with Tenofovir.
TipranavirTipranavir may increase the antiplatelet activities of Diflunisal.
TobramycinDiflunisal may decrease the excretion rate of Tobramycin which could result in a lower serum level and potentially a reduction in efficacy.
TorasemideDiflunisal may decrease the diuretic activities of Torasemide.
TositumomabThe risk or severity of adverse effects can be increased when Diflunisal is combined with Tositumomab.
TreprostinilThe risk or severity of adverse effects can be increased when Treprostinil is combined with Diflunisal.
TriamtereneDiflunisal may decrease the antihypertensive activities of Triamterene.
TrichlormethiazideThe therapeutic efficacy of Trichlormethiazide can be decreased when used in combination with Diflunisal.
UnoprostoneThe therapeutic efficacy of Unoprostone can be decreased when used in combination with Diflunisal.
UrokinaseDiflunisal may increase the anticoagulant activities of Urokinase.
ValsartanThe risk or severity of adverse effects can be increased when Valsartan is combined with Diflunisal.
VancomycinThe serum concentration of Vancomycin can be increased when it is combined with Diflunisal.
VenlafaxineVenlafaxine may increase the antiplatelet activities of Diflunisal.
VerteporfinDiflunisal may increase the photosensitizing activities of Verteporfin.
Vitamin EVitamin E may increase the antiplatelet activities of Diflunisal.
WarfarinDiflunisal may increase the anticoagulant activities of Warfarin.
Food Interactions
  • Avoid alcohol.
  • Food slightly delays rate of absorption with no effect on extent of absorption.
  • Take with food to reduce gastric irritation.

Targets

1. Prostaglandin G/H synthase 2

Kind: Protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Prostaglandin G/H synthase 2 P35354 Details

References:

  1. 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. Pubmed
  2. Jeske AH: COX-2 inhibitors and dental pain control. J Gt Houst Dent Soc. 1999 Nov;71(4):39-40. Pubmed
  3. 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. Pubmed
  4. 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. Pubmed
  5. 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. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Prostaglandin G/H synthase 1

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Prostaglandin G/H synthase 1 P23219 Details

References:

  1. 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. Pubmed
  2. 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. Pubmed
  3. 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. Pubmed

Enzymes

1. UDP-glucuronosyltransferase 1-8

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
UDP-glucuronosyltransferase 1-8 Q9HAW9 Details

References:

  1. 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. Pubmed

Carriers

1. Transthyretin

Kind: Protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Transthyretin P02766 Details

References:

  1. 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. Pubmed
  2. 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. Pubmed
  3. 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. Pubmed
  4. 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. Pubmed
  5. 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. Pubmed

2. Serum albumin

Kind: Protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Serum albumin P02768 Details

References:

  1. 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. Pubmed
  2. 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. Pubmed
  3. 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. Pubmed
  4. 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. Pubmed

Transporters

1. Solute carrier family 22 member 6

Kind: Protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 6 Q4U2R8 Details

References:

  1. 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. Pubmed
  2. 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. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on April 14, 2014 12:54