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Identification
NameSulindac
Accession NumberDB00605  (APRD01243)
TypeSmall Molecule
GroupsApproved
Description

Sulindac is a nonsteroidal anti-inflammatory agent (NSAIA) of the arylalkanoic acid class that is marketed in the U.S. by Merck as Clinoril. Like other NSAIAs, it may be used in the treatment of acute or chronic inflammatory conditions. Sulindac is a prodrug, derived from sulfinylindene, that is converted in vivo to an active sulfide compound by liver enzymes. The sulfide metabolite then undergoes enterohepatic circulation; it is excreted in the bile and then reabsorbed from the intestine. This is thought to help maintain constant blood levels with reduced gastrointestinal side effects. Some studies have shown sulindac to be relatively less irritating to the stomach than other NSAIA’s except for drugs of the cyclooxygenase-2 (COX-2) inhibitor class. The exact mechanism of its NSAIA properties is unknown, but it is thought to act on enzymes COX-1 and COX-2, inhibiting prostaglandin synthesis.

Structure
Thumb
Synonyms
SynonymLanguageCode
(Z)-5-Fluoro-2-methyl-1-((P-(methylsulfinyl)phenyl)methylene)-1H-indene-3-acetic acidNot AvailableNot Available
cis-5-Fluoro-2-methyl-1-((4-(methylsulfinyl)phenyl)methylene)-1H-indene-3-acetic acidNot AvailableNot Available
cis-5-Fluoro-2-methyl-1-((P-methylsulfinyl)benzylidene)indene-3-acetic acidNot AvailableNot Available
ClinorilNot AvailableNot Available
SulindacNot AvailableNot Available
SulindacoNot AvailableNot Available
SulindacumNot AvailableNot Available
Prescription ProductsNot Available
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Sulindactablet150 mgoralMylan Pharmaceuticals Inc.1993-06-22Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Sulindactablet200 mgoralMylan Pharmaceuticals Inc.1993-06-22Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Sulindactablet200 mgoralWatson Laboratories, Inc.1990-04-03Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Sulindactablet150 mgoralWatson Laboratories, Inc.1990-04-03Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Sulindactablet200 mgoralMajor Pharmaceuticals2009-09-04Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Sulindactablet150 mgoralMajor Pharmaceuticals2010-11-30Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Sulindactablet200 mgoralMajor Pharmaceuticals2010-11-30Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Sulindactablet200 mgoralSTAT Rx USA LLC2010-01-25Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Sulindactablet150 mgoralHeritage Pharmaceuticals Inc.2007-07-16Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Sulindactablet200 mgoralHeritage Pharmaceuticals Inc.2007-07-16Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Sulindactablet200 mgoralAidarex Pharmaceuticals LLC2010-01-25Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Sulindactablet150 mgoralAv Kare, Inc.2010-01-25Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Sulindactablet200 mgoralAv Kare, Inc.2010-01-25Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Sulindactablet200 mgoralEpic Pharma, LLC2010-01-25Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Sulindactablet150 mgoralEpic Pharma, LLC2010-01-25Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Sulindactablet200 mgoralLake Erie Medical DBA Quality Care Products LLC2010-06-23Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Sulindactablet200 mgoralUDL Laboratories, Inc.2011-03-18Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Sulindactablet200 mgoralH.J. Harkins Company, Inc.1990-04-03Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Sulindactablet150 mgoralMutual Pharmaceutical Company, Inc.2009-09-04Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Sulindactablet200 mgoralMutual Pharmaceutical Company, Inc.2009-09-04Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Sulindactablet200 mgoralState of Florida DOH Central Pharmacy2009-07-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Sulindactablet200 mgoralState of Florida DOH Central Pharmacy2009-07-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Sulindactablet150 mgoralState of Florida DOH Central Pharmacy2009-07-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Sulindactablet200 mgoralState of Florida DOH Central Pharmacy2013-01-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Sulindactablet150 mgoralRichmond Pharmaceuticals2009-09-04Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Sulindactablet200 mgoralRichmond Pharmaceuticals2009-09-04Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Sulindactablet150 mgoralPhysicians Total Care, Inc.2007-07-04Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Sulindactablet200 mgoralPhysicians Total Care, Inc.2007-07-05Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Sulindactablet200 mgoralPd Rx Pharmaceuticals, Inc.1990-04-03Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Sulindactablet150 mgoralGolden State Medical Supply, Inc.2010-01-25Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Sulindactablet200 mgoralGolden State Medical Supply, Inc.2010-01-25Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Sulindactablet200 mgoralbryant ranch prepack1990-04-03Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Sulindactablet150 mgoralbryant ranch prepack1990-04-03Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Sulindactablet200 mgoralCarilion Materials Management1990-04-03Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Sulindactablet200 mgoralCarilion Materials Management1990-04-03Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Over the Counter ProductsNot Available
International Brands
NameCompany
ClinorilMerck
Brand mixturesNot Available
SaltsNot Available
Categories
CAS number38194-50-2
WeightAverage: 356.411
Monoisotopic: 356.088243305
Chemical FormulaC20H17FO3S
InChI KeyMLKXDPUZXIRXEP-MFOYZWKCSA-N
InChI
InChI=1S/C20H17FO3S/c1-12-17(9-13-3-6-15(7-4-13)25(2)24)16-8-5-14(21)10-19(16)18(12)11-20(22)23/h3-10H,11H2,1-2H3,(H,22,23)/b17-9-
IUPAC Name
2-[(1Z)-5-fluoro-1-[(4-methanesulfinylphenyl)methylidene]-2-methyl-1H-inden-3-yl]acetic acid
SMILES
CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(C=C1)S(C)=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as indenes and isoindenes. These are compounds containing an indene moiety(which consists of a cyclopentadiene fused to a benzene ring), or a isoindene moiety (which consists of a cyclopentadiene fused to cyclohexadiene ring).
KingdomOrganic compounds
Super ClassBenzenoids
ClassIndenes and isoindenes
Sub ClassNot Available
Direct ParentIndenes and isoindenes
Alternative Parents
Substituents
  • Indene
  • Monocyclic benzene moiety
  • Aryl halide
  • Aryl fluoride
  • Sulfoxide
  • Sulfinyl compound
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organosulfur compound
  • Organooxygen compound
  • Organofluoride
  • Organohalogen compound
  • Carbonyl group
  • Aromatic homopolycyclic compound
Molecular FrameworkAromatic homopolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor acute or long-term use in the relief of signs and symptoms of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, acute painful shoulder (acute subacromial bursitis/supraspinatus tendinitis), and acute gouty arthritis.
PharmacodynamicsSulindac is a non-steroidal anti-inflammatory indene derivative, also possessing analgesic and antipyretic activities.
Mechanism of actionSulindac's exact mechanism of action is unknown. Its antiinflammatory effects are believed to be due to inhibition of both COX-1 and COX-2 which leads to the inhibition of prostaglandin synthesis. Antipyretic effects may be due to action on the hypothalamus, resulting in an increased peripheral blood flow, vasodilation, and subsequent heat dissipation.
AbsorptionApproximately 90% absorbed in humans following oral administration.
Volume of distributionNot Available
Protein bindingAt 1 mcg/ml concentrations, approximately 93% sulindac and 98% of its sulfide metabolite are bound to human serum albumin.
Metabolism

Undergoes two major biotransformations: reversible reduction to the sulfide metabolite, and irreversible oxidation to the sulfone metabolite. Sulindac and its sulfide and sulfone metabolites undergo extensive enterohepatic circulation. Available evidence indicates that the biological activity resides with the sulfide metabolite. Side chain hydroxylation and hydration of the double bond also occur.

SubstrateEnzymesProduct
Sulindac
Not Available
Sulindac sulfideDetails
Sulindac
Not Available
Sulindac sulfoneDetails
Route of eliminationSulindac is excreted in rat milk; concentrations in milk were 10 to 20% of those levels in plasma. It is not known if sulindac is excreted in human milk. Approximately 50% of the administered dose of sulindac is excreted in the urine with the conjugated sulfone metabolite accounting for the major portion. Hepatic metabolism is an important elimination pathway.
Half lifeThe mean half-life of sulindac is 7.8 hours while the mean half-life of the sulfide metabolite is 16.4 hours.
Clearance
  • Renal cl=68.12 +/- 27.56 mL/min [NORMAL (19-41 yrs)]
ToxicityAcute oral toxicity (LD50) in rats is 264 mg/kg. Cases of overdose have been reported and rarely, deaths have occurred. The following signs and symptoms may be observed following overdose: stupor, coma, diminished urine output and hypotension.
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+0.9937
Blood Brain Barrier+0.8325
Caco-2 permeable-0.8957
P-glycoprotein substrateNon-substrate0.5904
P-glycoprotein inhibitor INon-inhibitor0.5847
P-glycoprotein inhibitor IINon-inhibitor0.9949
Renal organic cation transporterNon-inhibitor0.8753
CYP450 2C9 substrateNon-substrate0.7715
CYP450 2D6 substrateNon-substrate0.8961
CYP450 3A4 substrateNon-substrate0.5629
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 substrateNon-inhibitor0.9071
CYP450 2D6 substrateNon-inhibitor0.9231
CYP450 2C19 substrateNon-inhibitor0.9025
CYP450 3A4 substrateNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5789
Ames testNon AMES toxic0.5451
CarcinogenicityNon-carcinogens0.6516
BiodegradationNot ready biodegradable1.0
Rat acute toxicity3.0989 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9768
hERG inhibition (predictor II)Non-inhibitor0.8671
Pharmacoeconomics
Manufacturers
  • Merck research laboratories div merck co inc
  • Epic pharma llc
  • Heritage pharmaceuticals inc
  • Mutual pharmaceutical co inc
  • Mylan pharmaceuticals inc
  • Sandoz inc
  • Teva pharmaceuticals usa inc
  • Watson laboratories inc
Packagers
Dosage forms
FormRouteStrength
Tabletoral150 mg
Tabletoral200 mg
Prices
Unit descriptionCostUnit
Sulindac powder17.36USD g
Clinoril 200 mg tablet1.58USD tablet
Sulindac 200 mg tablet1.23USD tablet
Sulindac 150 mg tablet1.0USD tablet
Apo-Sulin 200 mg Tablet0.51USD tablet
Novo-Sundac 200 mg Tablet0.51USD tablet
Nu-Sulindac 200 mg Tablet0.51USD tablet
Apo-Sulin 150 mg Tablet0.4USD tablet
Novo-Sundac 150 mg Tablet0.4USD tablet
Nu-Sulindac 150 mg Tablet0.4USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point183 °CPhysProp
water solubility3000 mg/LMERCK INDEX (1996); pH 7
logP3.42SANGSTER (1993)
pKa4.7MERCK INDEX (1996)
Predicted Properties
PropertyValueSource
Water Solubility0.0251 mg/mLALOGPS
logP2.96ALOGPS
logP2.93ChemAxon
logS-4.2ALOGPS
pKa (Strongest Acidic)4.09ChemAxon
pKa (Strongest Basic)-6.7ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area54.37 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity99.56 m3·mol-1ChemAxon
Polarizability37.2 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

Gary Piazza, Robert Reynolds, “Derivatives of sulindac, use thereof and preparation thereof.” U.S. Patent US20070244122, issued October 18, 2007.

US20070244122
General ReferenceNot Available
External Links
ATC CodesM01AB02
AHFS Codes
  • 28:08.04.92
PDB EntriesNot Available
FDA labelDownload (106 KB)
MSDSDownload (73.2 KB)
Interactions
Drug Interactions
Drug
AbciximabAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
AcenocoumarolAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
Acetylsalicylic acidNSAID (Nonselective) may enhance the adverse/toxic effect of Salicylates. An increased risk of bleeding may be associated with use of this combination. NSAID (Nonselective) may diminish the cardioprotective effect of Salicylates. Salicylates may decrease the serum concentration of NSAID (Nonselective). Exceptions: Choline Magnesium Trisalicylate.
AliskirenNonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Aliskiren. Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Aliskiren.
AlteplaseAgents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents.
AmikacinNonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants.
AnistreplaseAgents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents.
ApixabanAgents with Antiplatelet Properties may enhance the adverse/toxic effect of Apixaban. Specifically, the risk for bleeding may be increased.
ArbekacinNonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants.
Citric AcidAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
ColesevelamMay decrease the absorption of Nonsteroidal Anti-Inflammatory Agents.
Dabigatran etexilateAgents with Antiplatelet Properties may enhance the anticoagulant effect of Dabigatran Etexilate. Agents with Antiplatelet Properties may increase the serum concentration of Dabigatran Etexilate. This mechanism applies specifically to clopidogrel.
DalteparinAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
DasatinibMay enhance the anticoagulant effect of Agents with Antiplatelet Properties.
DeferasiroxNonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased.
Deoxycholic AcidAgents with Antiplatelet Properties may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased.
DesmopressinNonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Desmopressin.
DicoumarolAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
DigoxinNonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Digoxin.
Dimethyl sulfoxideMay decrease the metabolism of Sulindac. Specifically, the concentrations of the active sulfide metabolite are decreased.
Edetic AcidAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
EnoxaparinAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
EplerenoneNonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Eplerenone. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Eplerenone.
Ethyl biscoumacetateAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
FloctafenineMay enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents.
Fondaparinux sodiumAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
FramycetinNonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants.
GentamicinNonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants.
GlucosamineMay enhance the antiplatelet effect of Agents with Antiplatelet Properties.
HaloperidolNonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Haloperidol. Specifically including drowsiness and confusion.
HeparinAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
HydralazineNonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of HydrALAZINE.
IbritumomabAgents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab. Both agents may contribute to impaired platelet function and an increased risk of bleeding.
KanamycinNonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants.
MethotrexateNonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Methotrexate.
NeomycinNonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants.
NetilmicinNonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants.
ObinutuzumabAgents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased.
PemetrexedNSAID (Nonselective) may increase the serum concentration of PEMEtrexed.
PentoxifyllineMay enhance the antiplatelet effect of Agents with Antiplatelet Properties.
PhenindioneAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
PhenprocoumonAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
PorfimerPhotosensitizing Agents may enhance the photosensitizing effect of Porfimer.
PralatrexateNonsteroidal Anti-Inflammatory Agents may increase the serum concentration of PRALAtrexate. More specifically, NSAIDS may decrease the renal excretion of pralatrexate.
ProbenecidMay increase the serum concentration of Nonsteroidal Anti-Inflammatory Agents.
ReteplaseAgents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents.
RibostamycinNonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants.
RidogrelAgents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents.
RivaroxabanAgents with Antiplatelet Properties may enhance the anticoagulant effect of Rivaroxaban.
Salicylate-sodiumNSAID (Nonselective) may enhance the adverse/toxic effect of Salicylates. An increased risk of bleeding may be associated with use of this combination. NSAID (Nonselective) may diminish the cardioprotective effect of Salicylates. Salicylates may decrease the serum concentration of NSAID (Nonselective). Exceptions: Choline Magnesium Trisalicylate.
SpectinomycinNonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants.
StreptokinaseAgents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents.
StreptomycinNonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants.
SulodexideAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
TenecteplaseAgents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents.
TenofovirNonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Tenofovir.
TipranavirMay enhance the antiplatelet effect of Agents with Antiplatelet Properties.
TobramycinNonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants.
TreprostinilAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
UrokinaseAgents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents.
VancomycinNonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Vancomycin.
VerteporfinPhotosensitizing Agents may enhance the photosensitizing effect of Verteporfin.
Vitamin EMay enhance the antiplatelet effect of Agents with Antiplatelet Properties.
WarfarinAgents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
Food InteractionsNot Available

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. Giuliano F, Warner TD: Ex vivo assay to determine the cyclooxygenase selectivity of non-steroidal anti-inflammatory drugs. Br J Pharmacol. 1999 Apr;126(8):1824-30. Pubmed
  2. Molina MA, Sitja-Arnau M, Lemoine MG, Frazier ML, Sinicrope FA: Increased cyclooxygenase-2 expression in human pancreatic carcinomas and cell lines: growth inhibition by nonsteroidal anti-inflammatory drugs. Cancer Res. 1999 Sep 1;59(17):4356-62. Pubmed
  3. Yip-Schneider MT, Barnard DS, Billings SD, Cheng L, Heilman DK, Lin A, Marshall SJ, Crowell PL, Marshall MS, Sweeney CJ: Cyclooxygenase-2 expression in human pancreatic adenocarcinomas. Carcinogenesis. 2000 Feb;21(2):139-46. Pubmed
  4. Fosslien E: Biochemistry of cyclooxygenase (COX)-2 inhibitors and molecular pathology of COX-2 in neoplasia. Crit Rev Clin Lab Sci. 2000 Oct;37(5):431-502. Pubmed
  5. Taylor MT, Lawson KR, Ignatenko NA, Marek SE, Stringer DE, Skovan BA, Gerner EW: Sulindac sulfone inhibits K-ras-dependent cyclooxygenase-2 expression in human colon cancer cells. Cancer Res. 2000 Dec 1;60(23):6607-10. 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. Giuliano F, Warner TD: Ex vivo assay to determine the cyclooxygenase selectivity of non-steroidal anti-inflammatory drugs. Br J Pharmacol. 1999 Apr;126(8):1824-30. Pubmed
  2. Lim JT, Piazza GA, Han EK, Delohery TM, Li H, Finn TS, Buttyan R, Yamamoto H, Sperl GJ, Brendel K, Gross PH, Pamukcu R, Weinstein IB: Sulindac derivatives inhibit growth and induce apoptosis in human prostate cancer cell lines. Biochem Pharmacol. 1999 Oct 1;58(7):1097-107. Pubmed
  3. Soriano AF, Helfrich B, Chan DC, Heasley LE, Bunn PA Jr, Chou TC: Synergistic effects of new chemopreventive agents and conventional cytotoxic agents against human lung cancer cell lines. Cancer Res. 1999 Dec 15;59(24):6178-84. Pubmed
  4. Cheng ZJ, Tikkanen I, Vapaatalo H, Mervaala EM: Vascular effects of COX inhibition and AT1 receptor blockade in transgenic rats harboring mouse renin-2 gene. J Physiol Pharmacol. 2002 Dec;53(4 Pt 1):597-613. Pubmed
  5. Cheng ZJ, Finckenberg P, Louhelainen M, Merasto S, Tikkanen I, Vapaatalo H, Mervaala EM: Cardiovascular and renal effects of cyclooxygenase inhibition in transgenic rats harboring mouse renin-2 gene (TGR[mREN2]27). Eur J Pharmacol. 2003 Feb 14;461(2-3):159-69. Pubmed

3. Aldose reductase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Aldose reductase P15121 Details

References:

  1. Sharma YR, Vajpayee RB, Bhatnagar R, Mohan M, Azad RV, Kumar M, Nath R: Topical sulindac therapy in diabetic senile cataracts: cataract-IV. Indian J Ophthalmol. 1989 Jul-Sep;37(3):127-33. Pubmed
  2. Crabbe MJ, Freeman G, Halder AB, Bron AJ: The inhibition of bovine lens aldose reductase by Clinoril, its absorption into the human red cell and its effect on human red cell aldose reductase activity. Ophthalmic Res. 1985;17(2):85-9. Pubmed
  3. Chaudhry PS, Cabrera J, Juliani HR, Varma SD: Inhibition of human lens aldose reductase by flavonoids, sulindac and indomethacin. Biochem Pharmacol. 1983 Jul 1;32(13):1995-8. Pubmed
  4. Jacobson M, Sharma YR, Cotlier E, Hollander JD: Diabetic complications in lens and nerve and their prevention by sulindac or sorbinil: two novel aldose reductase inhibitors. Invest Ophthalmol Vis Sci. 1983 Oct;24(10):1426-9. Pubmed
  5. van der Sloot P, Mizisin A, Zochodne D: Sulindac in established experimental diabetes: a follow-up study. Can J Neurol Sci. 1995 Aug;22(3):198-201. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

4. Mitogen-activated protein kinase 3

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Mitogen-activated protein kinase 3 P27361 Details

References:

  1. Rice PL, Goldberg RJ, Ray EC, Driggers LJ, Ahnen DJ: Inhibition of extracellular signal-regulated kinase 1/2 phosphorylation and induction of apoptosis by sulindac metabolites. Cancer Res. 2001 Feb 15;61(4):1541-7. Pubmed
  2. Rice PL, Washington M, Schleman S, Beard KS, Driggers LJ, Ahnen DJ: Sulindac sulfide inhibits epidermal growth factor-induced phosphorylation of extracellular-regulated kinase 1/2 and Bad in human colon cancer cells. Cancer Res. 2003 Feb 1;63(3):616-20. Pubmed
  3. Rice PL, Beard KS, Driggers LJ, Ahnen DJ: Inhibition of extracellular-signal regulated kinases 1/2 is required for apoptosis of human colon cancer cells in vitro by sulindac metabolites. Cancer Res. 2004 Nov 15;64(22):8148-51. Pubmed
  4. Pangburn HA, Kraus H, Ahnen DJ, Rice PL: Sulindac metabolites inhibit epidermal growth factor receptor activation and expression. J Carcinog. 2005 Sep 2;4:16. Pubmed
  5. Rice PL, Peters SL, Beard KS, Ahnen DJ: Sulindac independently modulates extracellular signal-regulated kinase 1/2 and cyclic GMP-dependent protein kinase signaling pathways. Mol Cancer Ther. 2006 Mar;5(3):746-54. Pubmed

5. Peroxisome proliferator-activated receptor delta

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: negative modulator

Components

Name UniProt ID Details
Peroxisome proliferator-activated receptor delta Q03181 Details

References:

  1. He TC, Chan TA, Vogelstein B, Kinzler KW: PPARdelta is an APC-regulated target of nonsteroidal anti-inflammatory drugs. Cell. 1999 Oct 29;99(3):335-45. Pubmed
  2. Babbar N, Ignatenko NA, Casero RA Jr, Gerner EW: Cyclooxygenase-independent induction of apoptosis by sulindac sulfone is mediated by polyamines in colon cancer. J Biol Chem. 2003 Nov 28;278(48):47762-75. Epub 2003 Sep 23. Pubmed
  3. Jarvis MC, Gray TJ, Palmer CN: Both PPARgamma and PPARdelta influence sulindac sulfide-mediated p21WAF1/CIP1 upregulation in a human prostate epithelial cell line. Oncogene. 2005 Dec 8;24(55):8211-5. Pubmed
  4. Kim DJ, Prabhu KS, Gonzalez FJ, Peters JM: Inhibition of chemically induced skin carcinogenesis by sulindac is independent of peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta). Carcinogenesis. 2006 May;27(5):1105-12. Epub 2006 Jan 16. Pubmed
  5. Liou JY, Ghelani D, Yeh S, Wu KK: Nonsteroidal anti-inflammatory drugs induce colorectal cancer cell apoptosis by suppressing 14-3-3epsilon. Cancer Res. 2007 Apr 1;67(7):3185-91. Pubmed

6. Prostaglandin D2 receptor 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Prostaglandin D2 receptor 2 Q9Y5Y4 Details

References:

  1. Hata AN, Lybrand TP, Marnett LJ, Breyer RM: Structural determinants of arylacetic acid nonsteroidal anti-inflammatory drugs necessary for binding and activation of the prostaglandin D2 receptor CRTH2. Mol Pharmacol. 2005 Mar;67(3):640-7. Epub 2004 Nov 24. Pubmed

Enzymes

1. Cytochrome P450 1A1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 1A1 P04798 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 1A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 1A2 P05177 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

Carriers

1. Serum albumin

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Serum albumin P02768 Details

References:

  1. Russeva VN, Zhivkova ZD: Molecular basis of sulindac competition with specific markers for the major binding sites on human serum albumin. Arzneimittelforschung. 2003;53(3):174-81. Pubmed
  2. Shams-Eldeen MA, Vallner JJ, Needham TE: Interaction of sulindac and metabolite with human serum albumin. J Pharm Sci. 1978 Aug;67(8):1077-80. Pubmed
  3. Zhivkova ZD, Russeva VN: Thermodynamic characterization of the binding process of sulindac to human serum albumin. Arzneimittelforschung. 2003;53(1):53-6. 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. Kuze K, Graves P, Leahy A, Wilson P, Stuhlmann H, You G: Heterologous expression and functional characterization of a mouse renal organic anion transporter in mammalian cells. J Biol Chem. 1999 Jan 15;274(3):1519-24. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:11