NAV

Sulindac

Identification

Summary

Sulindacis an NSAID used to treat osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, acute subacromial bursitis or supraspinatus tendinitis, and acute gouty arthritis.

总的来说ic Name
Sulindac
DrugBank Accession Number
DB00605
Background

Sulindac is a nonsteroidal anti-inflammatory drug (NSAID) of the arylalkanoic acid class that is marketed by Merck under the brand name Clinoril. Like other NSAIDs, it may be used in the treatment of acute or chronic inflammatory conditions. Sulindac is a prodrug, derived from sulfinylindene, that is convertedin vivoto an active sulfide compound by liver enzymes. There is evidence from some studies that sulindac may be associated with fewer gastrointestinal side effects than other NSAIDs, except for the cyclooxygenase-2 (COX-2) inhibitor drug class. This may be due to the sulfide metabolite undergoing enterohepatic circulation thus maintaining constant blood levels of the compound without inducing gastrointestinal effects, where the drug is excreted in the bile and then reabsorbed from the intestines. While its full mechanism of action is not fully understood, sulindac is thought to primarily mediate its action by inhibiting prostaglandin synthesis by inhibiting COX-1 and COX-2.

Type
Small Molecule
Groups
Approved, Investigational
Structure
 3D
Similar Structures
Weight
Average: 356.411
Monoisotopic: 356.088243305
Chemical Formula
C20H17FO3S
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

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.

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Associated Conditions
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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.

Target Actions Organism
AProstaglandin G/H synthase 2
inhibitor
 Humans
UProstaglandin G/H synthase 1
inhibitor
 Humans
UAldose reductase
inhibitor
 Humans
UMitogen-activated protein kinase 3
inhibitor
 Humans
UPeroxisome proliferator-activated receptor delta
negative modulator
 Humans
UProstaglandin D2 receptor 2
antagonist
 Humans
UAldo-keto reductase family 1 member B10
inhibitor
 Humans
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.

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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)]
Adverse Effects
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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.

Pathways
Pathway Category
Sulindac Action Pathway Drug action
Pharmacogenomic Effects/ADRsBrowse all" title="" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Not Available

Interactions

Drug InteractionsLearn More" title="" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
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
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interactions in your software
Abacavir Sulindac 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 Sulindac is combined with Abciximab.
Acebutolol Sulindac may decrease the antihypertensive activities of Acebutolol.
Aceclofenac 不利影响的风险或严重性可以公司reased when Sulindac is combined with Aceclofenac.
Acemetacin 不利影响的风险或严重性可以公司reased when Sulindac is combined with Acemetacin.
Acenocoumarol The risk or severity of bleeding and hemorrhage can be increased when Sulindac is combined with Acenocoumarol.
Acetaminophen 不利影响的风险或严重性可以公司reased when Acetaminophen is combined with Sulindac.
Acetohexamide protein binding of Acetohexamide can be decreased when combined with Sulindac.
Acetylsalicylic acid The therapeutic efficacy of Acetylsalicylic acid can be decreased when used in combination with Sulindac.
Aclidinium Sulindac may decrease the excretion rate of Aclidinium which could result in a higher serum level.
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Food Interactions
  • Avoid alcohol. Ingesting alcohol may increase the risk of gastrointestinal bleeding.
  • Take with food.

Products

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Product Ingredients
Ingredient UNII CAS InChI Key
Sulindac sodium NJV14I2XPC 63804-15-9 YMXUJDLCLXHYBO-WPTDRQDKSA-M
Product Images
Brand Name Prescription Products
Name Dosage Strength Route 贴标机 Marketing Start Marketing End Region Image
Clinoril Tablet 200 mg/1 Oral Merck Sharp & Dohme Limited 1978-09-27 2012-03-31 US flag
Clinoril Tablet 150 mg/1 Oral Merck & Co., Inc. 2007-02-01 2007-02-01 US flag
Clinoril Tab 150mg Tablet 150 mg / tab Oral Merck Frosst Canada & Cie, Merck Frosst Canada & Co. 1979-12-31 1998-08-14 Canada flag
Clinoril Tab 200mg Tablet 200 mg / tab Oral Merck Frosst Canada & Cie, Merck Frosst Canada & Co. 1979-12-31 1998-08-14 Canada flag
Sulindac-150 Tab 150mg Tablet 150 mg Oral Pro Doc Limitee 1989-12-31 2009-07-23 Canada flag
Sulindac-200 Tab 200mg Tablet 200 mg Oral Pro Doc Limitee 1989-12-31 2009-07-23 Canada flag
总的来说ic Prescription Products
Name Dosage Strength Route 贴标机 Marketing Start Marketing End Region Image
Apo-sulin Tab 150mg Tablet 150 mg Oral Apotex Corporation 1988-12-31 2019-12-02 Canada flag
Apo-sulin标签200毫克 Tablet 200 mg Oral Apotex Corporation 1988-12-31 2019-12-02 Canada flag
Nu-sulindac Tab 150mg Tablet 150 mg Oral Nu Pharm Inc 1994-12-31 2012-09-04 Canada flag
Nu-sulindac Tab 200mg Tablet 200 mg Oral Nu Pharm Inc 1994-12-31 2012-09-04 Canada flag
Penta-sulindac Tablet 150 mg / tab Oral Pentapharm Ltd. Not applicable Not applicable Canada flag
Penta-sulindac Tablet 200 mg / tab Oral Pentapharm Ltd. Not applicable Not applicable Canada flag
Sulindac Tablet 150 mg/1 Oral Physicians Total Care, Inc. 2007-07-04 Not applicable US flag
Sulindac Tablet 200 mg/1 Oral Major 2009-09-04 2013-01-31 US flag
Sulindac Tablet 150 mg/1 Oral Golden State Medical Supply, Inc. 1991-04-17 2020-01-29 US flag
Sulindac Tablet 200 mg/1 Oral Av Kare, Inc. 2010-01-25 2015-02-20 US flag

Categories

ATC Codes
M01AB02 — Sulindac
Drug Categories
Chemical TaxonomyProvided byClassyfire
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
子课
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
Aromatic homopolycyclic compound/Aryl fluoride/Aryl halide/Carbonyl group/Carboxylic acid/Carboxylic acid derivative/Hydrocarbon derivative/Indene/Monocarboxylic acid or derivatives/Monocyclic benzene moiety
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
或ganofluorine compound, monocarboxylic acid, sulfoxide (CHEBI:9352)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
184SNS8VUH
CAS number
38194-50-2
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

References

Synthesis Reference

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

 US20070244122
总的来说al References
Not Available
Human Metabolome Database
HMDB0014743
KEGG Drug
D00120
KEGG Compound
C01531
PubChem Compound
1548887
PubChem Substance
46506570
ChemSpider
1265915
BindingDB
50103504
RxNav
10237
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
FDA label
Download (106 KB)
MSDS
Download (73.2 KB)

Clinical Trials

Clinical TrialsLearn More" title="" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count
3 Completed Prevention Precancerous Conditions 1
3 Completed Treatment Familial Adenomatous Polyposis (FAP) 1
3 Recruiting Prevention 肿瘤、结直肠 1
3 Withdrawn Treatment Familial Adenomatous Polyposis (FAP) 1
2 Active Not Recruiting Treatment Cancer/High Blood Pressure (Hypertension)/Inflammation/Pain 1
2 Completed Prevention Adenomatous Polyposis Coli 1
2 Completed Prevention Colorectal Cancer 1
2 Completed Prevention Lung Cancer, Nonsmall Cell, Stage I/Precancerous Conditions/Tobacco Use Disorders 1
2 Completed Prevention Malignant Neoplasm of Colon/Precancerous Conditions/Rectal Carcinoma 1
2 Completed Prevention Precancerous Conditions 1

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
Form Route Strength
Suppository
Tablet Oral
Tablet Oral 150 mg / tab
Tablet Oral 200 mg / tab
Tablet Oral 150 mg/1
Tablet Oral 200 mg/1
Tablet Oral 200 mg
Tablet Oral 150 mg
Prices
Unit description Cost Unit
Sulindac powder 17.36USD g
Clinoril 200 mg tablet 1.58USD tablet
Sulindac 200 mg tablet 1.23USD tablet
Sulindac 150 mg tablet 1.0USD tablet
Apo-Sulin 200 mg Tablet 0.51USD tablet
Novo-Sundac 200 mg Tablet 0.51USD tablet
Nu-Sulindac 200 mg Tablet 0.51USD tablet
Apo-Sulin 150 mg Tablet 0.4USD tablet
Novo-Sundac 150 mg Tablet 0.4USD tablet
Nu-Sulindac 150 mg Tablet 0.4USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
Property Value Source
melting point (°C) 183 °C PhysProp
water solubility 3000 mg/L MERCK INDEX (1996); pH 7
logP 3.42 SANGSTER (1993)
pKa 4.7 MERCK INDEX (1996)
Predicted Properties
Property Value Source
Water Solubility 0.0251 mg/mL ALOGPS
logP 2.96 ALOGPS
logP 2.93 ChemAxon
logS -4.2 ALOGPS
pKa (Strongest Acidic) 4.09 ChemAxon
pKa (Strongest Basic) -8.1 ChemAxon
Physiological Charge -1 ChemAxon
Hydrogen Acceptor Count 3 ChemAxon
Hydrogen Donor Count 1 ChemAxon
Polar Surface Area 54.37 Å2 ChemAxon
Rotatable Bond Count 4 ChemAxon
Refractivity 99.56 m3·mol-1 ChemAxon
Polarizability 37.21 Å3 ChemAxon
Number of Rings 3 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 + 0.9937
Blood Brain Barrier + 0.8325
Caco-2 permeable - 0.8957
P-glycoprotein substrate Non-substrate 0.5904
P-glycoprotein inhibitor I Non-inhibitor 0.5847
P-glycoprotein inhibitor II Non-inhibitor 0.9949
Renal organic cation transporter Non-inhibitor 0.8753
CYP450 2C9 substrate Non-substrate 0.7715
CYP450 2D6 substrate Non-substrate 0.8961
CYP450 3A4 substrate Non-substrate 0.5629
CYP450 1A2 substrate Inhibitor 0.9107
CYP450 2C9 inhibitor Non-inhibitor 0.9071
CYP450 2D6 inhibitor Non-inhibitor 0.9231
CYP450 2C19 inhibitor Non-inhibitor 0.9025
CYP450 3A4 inhibitor Non-inhibitor 0.8309
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.5789
Ames test Non AMES toxic 0.5451
Carcinogenicity Non-carcinogens 0.6516
Biodegradation Not ready biodegradable 1.0
Rat acute toxicity 3.0989 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9768
hERG inhibition (predictor II) Non-inhibitor 0.8671
ADMET data is predicted usingadmetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
Spectrum Spectrum Type Splash Key
Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
LC-MS/MS Spectrum - LC-ESI-qTof , Positive LC-MS/MS Not Available
LC-MS/MS Spectrum - LC-ESI-QQ , positive LC-MS/MS splash10-0a4i-0019000000-fec3a7dbf1ba6b64f03e
LC-MS/MS Spectrum - LC-ESI-QQ , positive LC-MS/MS splash10-0a4i-0019000000-6a9b19701aa1af58166d
LC-MS/MS Spectrum - LC-ESI-QQ , positive LC-MS/MS splash10-001l-0095000000-1aef30e1f36f3fcc9ea2
LC-MS/MS Spectrum - LC-ESI-QQ , positive LC-MS/MS splash10-001j-0090000000-4f30705a14fab7bb25e0
LC-MS/MS Spectrum - LC-ESI-QQ , positive LC-MS/MS splash10-001i-0090000000-8bf873219e6e4353be1e
LC-MS/MS Spectrum - LC-ESI-IT , positive LC-MS/MS splash10-000y-0095000000-0a507959838acf3f73cb
MS/MS Spectrum - , positive LC-MS/MS splash10-0a4i-0059000000-3ad0cecc4eb73cce225e
MS/MS Spectrum - , positive LC-MS/MS splash10-0a4i-0069000000-be643d55172bd2292511
MS/MS Spectrum - , positive LC-MS/MS splash10-001j-1290000000-33b23a68145a3ef2000c

Targets

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Details 1.Prostaglandin G/H synthase 2
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
总的来说al 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
分子量
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Details 2.Prostaglandin G/H synthase 1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
总的来说al 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
分子量
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Details 3.Aldose reductase
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
总的来说al 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
分子量
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Details 4.Mitogen-activated protein kinase 3
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
总的来说al 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
分子量
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  5. 大米PL,彼得斯SL,胡子KS Ahnen DJ:我苏灵大ndependently modulates extracellular signal-regulated kinase 1/2 and cyclic GMP-dependent protein kinase signaling pathways. Mol Cancer Ther. 2006 Mar;5(3):746-54. [Article]
Details 5.Peroxisome proliferator-activated receptor delta
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Negative modulator
总的来说al 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
分子量
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Details 6.Prostaglandin D2 receptor 2
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
总的来说al 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
分子量
43267.15 Da
References
  1. 要么,Lybrand TP, Marnett LJ,布雷耶RM:结构体ural 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. [Article]
Details 7.Aldo-keto reductase family 1 member B10
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
总的来说al 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
分子量
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. [Article]

Enzymes

Details 1.Cytochrome P450 1A1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
总的来说al 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
分子量
58164.815 Da
References
  1. Ciolino HP, MacDonald CJ, Memon OS, Bass SE, Yeh GC: Sulindac regulates the aryl hydrocarbon receptor-mediated expression of Phase 1 metabolic enzymes in vivo and in vitro. Carcinogenesis. 2006 Aug;27(8):1586-92. doi: 10.1093/carcin/bgi359. Epub 2006 Mar 10. [Article]

Carriers

Details 1.Serum albumin
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
总的来说al 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
分子量
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. [Article]
  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. [Article]
  3. Zhivkova ZD, Russeva VN: Thermodynamic characterization of the binding process of sulindac to human serum albumin. Arzneimittelforschung. 2003;53(1):53-6. [Article]

Transporters

Details 1.Solute carrier family 22 member 6
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
总的来说al 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
分子量
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. [Article]

Drug created at June 13, 2005 13:24 / Updated at October 13, 2022 04:06