Identification

Name
Sulindac
Accession Number
DB00605  (APRD01243)
Type
Small Molecule
Groups
Approved, Investigational
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
  • (Z)-5-Fluoro-2-methyl-1-((P-(methylsulfinyl)phenyl)methylene)-1H-indene-3-acetic acid
  • cis-5-Fluoro-2-methyl-1-((4-(methylsulfinyl)phenyl)methylene)-1H-indene-3-acetic acid
  • cis-5-Fluoro-2-methyl-1-((P-methylsulfinyl)benzylidene)indene-3-acetic acid
  • Sulindac
  • Sulindaco
  • Sulindacum
Product Ingredients
IngredientUNIICASInChI Key
Sulindac sodiumNJV14I2XPC63804-15-9YMXUJDLCLXHYBO-WPTDRQDKSA-M
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ClinorilTablet150 mg/1OralMerck & Co., Inc.2007-02-012007-02-01Us
ClinorilTablet200 mg/1OralMerck Sharp & Dohme Limited1978-09-272012-03-31Us
Clinoril Tab 150mgTablet150 mgOralMerck Frosst Canada & Cie, Merck Frosst Canada & Co.1979-12-311998-08-14Canada
Clinoril Tab 200mgTablet200 mgOralMerck Frosst Canada & Cie, Merck Frosst Canada & Co.1979-12-311998-08-14Canada
Sulindac-150 Tab 150mgTablet150 mgOralPro Doc Limitee1989-12-312009-07-23Canada
Sulindac-200 Tab 200mgTablet200 mgOralPro Doc Limitee1989-12-312009-07-23Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-sulin Tab 150mgTablet150 mgOralApotex Corporation1988-12-31Not applicableCanada
Apo-sulin Tab 200mgTablet200 mgOralApotex Corporation1988-12-31Not applicableCanada
Nu-sulindac Tab 150mgTablet150 mgOralNu Pharm Inc1994-12-312012-09-04Canada
Nu-sulindac Tab 200mgTablet200 mgOralNu Pharm Inc1994-12-312012-09-04Canada
Penta-sulindacTablet200 mgOralPentapharm Ltd.Not applicableNot applicableCanada
Penta-sulindacTablet150 mgOralPentapharm Ltd.Not applicableNot applicableCanada
SulindacTablet200 mg/1OralH.J. Harkins Company1990-04-03Not applicableUs
SulindacTablet200 mg/1OralPuraCap Laboratories LLC dba Blu Pharmaceuticals2016-11-14Not applicableUs
SulindacTablet150 mg/1OralMylan Pharmaceuticals1993-06-22Not applicableUs
SulindacTablet200 mg/1OralA-S Medication Solutions2010-01-25Not applicableUs50090 052920180913 8702 1qtyyy
International/Other Brands
Clinoril (Merck)
Categories
UNII
184SNS8VUH
CAS number
38194-50-2
Weight
Average: 356.411
Monoisotopic: 356.088243305
Chemical Formula
C20H17FO3S
InChI Key
MLKXDPUZXIRXEP-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

Pharmacology

Indication

For 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.

Associated Conditions
Pharmacodynamics

Sulindac is a non-steroidal anti-inflammatory indene derivative, also possessing analgesic and antipyretic activities.

Mechanism of action

Sulindac'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.

TargetActionsOrganism
AProstaglandin G/H synthase 2
inhibitor
Human
UProstaglandin G/H synthase 1
inhibitor
Human
UAldose reductase
inhibitor
Human
UMitogen-activated protein kinase 3
inhibitor
Human
UPeroxisome proliferator-activated receptor delta
negative modulator
Human
UProstaglandin D2 receptor 2
antagonist
Human
UAldo-keto reductase family 1 member B10
inhibitor
Human
Absorption

Approximately 90% absorbed in humans following oral administration.

Volume of distribution
Not Available
Protein binding

At 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.

Route of elimination

Sulindac 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 life

The 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)]
Toxicity

Acute 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
Pathways
PathwayCategory
Sulindac Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinSulindac may increase the anticoagulant activities of (R)-warfarin.
(S)-WarfarinSulindac may increase the anticoagulant activities of (S)-Warfarin.
4-hydroxycoumarinSulindac may increase the anticoagulant activities of 4-hydroxycoumarin.
AcebutololSulindac may decrease the antihypertensive activities of Acebutolol.
AceclofenacThe risk or severity of adverse effects can be increased when Sulindac is combined with Aceclofenac.
AcemetacinThe risk or severity of adverse effects can be increased when Sulindac is combined with Acemetacin.
AcenocoumarolSulindac may increase the anticoagulant activities of Acenocoumarol.
AcetaminophenSulindac may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
AcetohexamideThe protein binding of Acetohexamide can be decreased when combined with Sulindac.
Acetylsalicylic acidThe risk or severity of adverse effects can be increased when Sulindac is combined with Acetylsalicylic acid.
Food Interactions
Not 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 References
Not Available
External Links
Human Metabolome Database
HMDB0014743
KEGG Drug
D00120
KEGG Compound
C01531
PubChem Compound
1548887
PubChem Substance
46506570
ChemSpider
1265915
BindingDB
50012899
ChEBI
9352
ChEMBL
CHEMBL15770
Therapeutic Targets Database
DAP000569
PharmGKB
PA451565
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Sulindac
ATC Codes
M01AB02 — Sulindac
AHFS Codes
  • 28:08.04.92 — Other Nonsteroidal Antiimflammatory Agents
FDA label
Download (106 KB)
MSDS
Download (73.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedPreventionCancer, Breast1
2Active Not RecruitingTreatmentDesmoid Tumors1
2CompletedPreventionAdenomatous Polyposis Coli1
2CompletedPreventionMalignant Neoplasm of Colon / Precancerous Conditions / Rectal Carcinoma1
2CompletedPreventionPrecancerous Conditions1
2CompletedPreventionPrecancerous Conditions / Stage I Non-Small Cell Lung Cancer / Tobacco Use Disorders1
2CompletedTreatmentCancer, Breast1
2CompletedTreatmentMelanoma (Skin)1
2CompletedTreatmentSquamous Cell Carcinoma of the Head and Neck (SCCHN)1
2RecruitingPreventionCancers / High Blood Pressure (Hypertension) / Inflammatory Reaction / Pain1
2TerminatedPreventionColorectal Cancers1
2TerminatedTreatmentColorectal Adenocarcinoma / Colorectal Cancers / Liver Metastasis1
2Unknown StatusPreventionAdenomatous Polyposis Coli1
2WithdrawnDiagnosticFocus of Study: Drug Response Biomarkers, Chemoprevention, Neoplasms1
2WithdrawnTreatmentLeukemia Acute Myeloid Leukemia (AML)1
3Active Not RecruitingTreatmentFamilial Adenomatous Polyposis (FAP)1
3CompletedPreventionPrecancerous Conditions1
Not AvailableActive Not RecruitingTreatmentNeoplasms, Benign / Oral Leukoplakia1
Not AvailableCompletedPreventionUnspecified Adult Solid Tumor, Protocol Specific1
Not AvailableTerminatedPreventionAberrant Crypt Foci1
Not AvailableTerminatedPreventionColorectal Cancers1

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
  • A-S Medication Solutions LLC
  • Avkare Incorporated
  • Bryant Ranch Prepack
  • Dept Health Central Pharmacy
  • DHHS Program Support Center Supply Service Center
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Endo Pharmaceuticals Inc.
  • Epic Pharma LLC
  • Golden State Medical Supply Inc.
  • Group Health Cooperative
  • H.J. Harkins Co. Inc.
  • Heartland Repack Services LLC
  • Heritage Pharmaceuticals
  • Innoviant Pharmacy Inc.
  • Kaiser Foundation Hospital
  • Keltman Pharmaceuticals Inc.
  • Major Pharmaceuticals
  • Merck & Co.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mutual Pharmaceutical Co.
  • Mylan
  • Nucare Pharmaceuticals Inc.
  • PD-Rx Pharmaceuticals Inc.
  • Pharmedix
  • Physicians Total Care Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Prescription Dispensing Service Inc.
  • Qualitest
  • Richmond Pharmacy
  • Southwood Pharmaceuticals
  • Spectrum Pharmaceuticals
  • St Mary's Medical Park Pharmacy
  • Stat Rx Usa
  • Tya Pharmaceuticals
  • UDL Laboratories
  • Va Cmop Dallas
  • Watson Pharmaceuticals
Dosage forms
FormRouteStrength
TabletOral150 mg/1
TabletOral200 mg/1
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.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)183 °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 RuleNoChemAxon
MDDR-like RuleNoChemAxon
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 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-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
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0a4i-0019000000-fec3a7dbf1ba6b64f03e
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0a4i-0019000000-6a9b19701aa1af58166d
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-001l-0095000000-1aef30e1f36f3fcc9ea2
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-001j-0090000000-4f30705a14fab7bb25e0
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-001i-0090000000-8bf873219e6e4353be1e
LC-MS/MS Spectrum - LC-ESI-IT , positiveLC-MS/MSsplash10-000y-0095000000-0a507959838acf3f73cb
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0a4i-0059000000-3ad0cecc4eb73cce225e
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0a4i-0069000000-be643d55172bd2292511
MS/MS Spectrum - , positiveLC-MS/MSsplash10-001j-1290000000-33b23a68145a3ef2000c

Taxonomy

Description
This 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).
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Indenes and isoindenes
Sub Class
Not Available
Direct Parent
Indenes and isoindenes
Alternative Parents
Phenyl sulfoxides / Aryl fluorides / Sulfoxides / Sulfinyl compounds / Monocarboxylic acids and derivatives / Carboxylic acids / Organofluorides / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Phenyl sulfoxide / Indene / Aryl fluoride / Aryl halide / Monocyclic benzene moiety / Sulfoxide / Sulfinyl compound / Carboxylic acid derivative / Carboxylic acid / Monocarboxylic acid or derivatives
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
organofluorine compound, monocarboxylic acid, sulfoxide (CHEBI:9352)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and...
Gene Name
PTGS2
Uniprot ID
P35354
Uniprot Name
Prostaglandin G/H synthase 2
Molecular Weight
68995.625 Da
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:10372826]
  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:10485483]
  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:10657949]
  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:11078056]
  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:11118042]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gas...
Gene Name
PTGS1
Uniprot ID
P23219
Uniprot Name
Prostaglandin G/H synthase 1
Molecular Weight
68685.82 Da
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:10372826]
  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:10484067]
  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:10626810]
  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:12512695]
  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:12586211]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Glyceraldehyde oxidoreductase activity
Specific Function
Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols with a broad range of catalytic efficiencies.
Gene Name
AKR1B1
Uniprot ID
P15121
Uniprot Name
Aldose reductase
Molecular Weight
35853.125 Da
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:2632448]
  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:3920599]
  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:6409111]
  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:6413448]
  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:8529171]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Phosphatase binding
Specific Function
Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK ca...
Gene Name
MAPK3
Uniprot ID
P27361
Uniprot Name
Mitogen-activated protein kinase 3
Molecular Weight
43135.16 Da
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:11245463]
  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:12566304]
  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:15548677]
  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:16138927]
  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:16546990]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Negative modulator
General Function
Zinc ion binding
Specific Function
Ligand-activated transcription factor. Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Has a preference for poly-unsaturated fatty acids, such as gamma-lin...
Gene Name
PPARD
Uniprot ID
Q03181
Uniprot Name
Peroxisome proliferator-activated receptor delta
Molecular Weight
49902.99 Da
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:10555149]
  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:14506281]
  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:16091736]
  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:16418176]
  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:17409426]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Prostaglandin j receptor activity
Specific Function
Receptor for prostaglandin D2 (PGD2). Coupled to the G(i)-protein. Receptor activation may result in pertussis toxin-sensitive decreases in cAMP levels and Ca(2+) mobilization. PI3K signaling is al...
Gene Name
PTGDR2
Uniprot ID
Q9Y5Y4
Uniprot Name
Prostaglandin D2 receptor 2
Molecular Weight
43267.15 Da
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:15563582]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Retinal dehydrogenase activity
Specific Function
Acts as all-trans-retinaldehyde reductase. Can efficiently reduce aliphatic and aromatic aldehydes, and is less active on hexoses (in vitro). May be responsible for detoxification of reactive aldeh...
Gene Name
AKR1B10
Uniprot ID
O60218
Uniprot Name
Aldo-keto reductase family 1 member B10
Molecular Weight
36019.295 Da
References
  1. Cousido-Siah A, Ruiz FX, Crespo I, Porte S, Mitschler A, Pares X, Podjarny A, Farres J: Structural analysis of sulindac as an inhibitor of aldose reductase and AKR1B10. Chem Biol Interact. 2015 Jun 5;234:290-6. doi: 10.1016/j.cbi.2014.12.018. Epub 2014 Dec 20. [PubMed:25532697]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Vitamin d 24-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A1
Uniprot ID
P04798
Uniprot Name
Cytochrome P450 1A1
Molecular Weight
58164.815 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
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:12705172]
  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:671241]
  3. Zhivkova ZD, Russeva VN: Thermodynamic characterization of the binding process of sulindac to human serum albumin. Arzneimittelforschung. 2003;53(1):53-6. [PubMed:12608015]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
Molecular Weight
61815.78 Da
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:9880528]

Drug created on June 13, 2005 07:24 / Updated on October 16, 2018 08:28