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Details

Stereochemistry RACEMIC
Molecular Formula C20H17FO3S
Molecular Weight 356.411
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of SULINDAC

SMILES

C[S+]([O-])C1=CC=C(\C=C2\C(C)=C(CC(O)=O)C3=C2C=CC(F)=C3)C=C1

InChI

InChIKey=MLKXDPUZXIRXEP-MFOYZWKCSA-N
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-

HIDE SMILES / InChI

Molecular Formula C20H17FO3S
Molecular Weight 356.411
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Description
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/017911s073lbl.pdf

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.

CNS Activity

Curator's Comment: Sulindac penetrates the blood-brain and placental barriers. Concentrations in brain did not exceed 4% of those in plasma.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
SULINDAC

Approved Use

CLINORIL is indicated for acute or long-term use in the relief of signs and symptoms of the following: 1. Osteoarthritis 2. Rheumatoid arthritis** 3. Ankylosing spondylitis 4. Acute painful shoulder (Acute subacromial bursitis/supraspinatus tendinitis) 5. Acute gouty arthritis

Launch Date

5.7326397E11
Primary
SULINDAC

Approved Use

CLINORIL is indicated for acute or long-term use in the relief of signs and symptoms of the following: 1. Osteoarthritis 2. Rheumatoid arthritis** 3. Ankylosing spondylitis 4. Acute painful shoulder (Acute subacromial bursitis/supraspinatus tendinitis) 5. Acute gouty arthritis

Launch Date

5.7326397E11
Primary
SULINDAC

Approved Use

CLINORIL is indicated for acute or long-term use in the relief of signs and symptoms of the following: 1. Osteoarthritis 2. Rheumatoid arthritis** 3. Ankylosing spondylitis 4. Acute painful shoulder (Acute subacromial bursitis/supraspinatus tendinitis) 5. Acute gouty arthritis

Launch Date

5.7326397E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
11.4 μg/mL
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
SULINDAC plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
9.21 μg/mL
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
SULINDAC plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
40.8 μg × h/mL
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
SULINDAC plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
2.95 h
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
SULINDAC plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
7.8 h
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
SULINDAC plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
6.9%
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
SULINDAC plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
PubMed

PubMed

TitleDatePubMed
Chemoprevention of esophageal adenocarcinoma by COX-2 inhibitors in an animal model of Barrett's esophagus.
2002 Apr
The influence of sulindac on patients with primary biliary cirrhosis that responds incompletely to ursodeoxycholic acid: a pilot study.
2002 Dec
Effects of long-term administration of sulindac on APC mRNA and apoptosis in colons of rats treated with azoxymethane.
2002 Nov
Interactions of human organic anion transporters and human organic cation transporters with nonsteroidal anti-inflammatory drugs.
2002 Nov
Novel detection and differential utilization of a c-myc transcriptional block in colon cancer chemoprevention.
2002 Nov 1
Effect of sulindac treatment for attenuated familial adenomatous polyposis with a new germline APC mutation at codon 161: report of a case.
2002 Oct
Discovery of molecular mechanisms of neuroprotection using cell-based bioassays and oligonucleotide arrays.
2002 Oct 29
A mouse model of human oral-esophageal cancer.
2002 Sep
Altered expression of c-myc, p16 and p27 in rat colon tumors and its reversal by short-term treatment with chemopreventive agents.
2002 Sep
Response of Apc(min) and A33 (delta N beta-cat) mutant mice to treatment with tea, sulindac, and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP).
2002 Sep 30
Sulindac sulfide inhibits epidermal growth factor-induced phosphorylation of extracellular-regulated kinase 1/2 and Bad in human colon cancer cells.
2003 Feb 1
Cardiovascular and renal effects of cyclooxygenase inhibition in transgenic rats harboring mouse renin-2 gene (TGR[mREN2]27).
2003 Feb 14
Cyclooxygenase-independent induction of apoptosis by sulindac sulfone is mediated by polyamines in colon cancer.
2003 Nov 28
Nutritional-pharmacological combinations--a novel approach to reducing colon cancer incidence.
2004 Aug
Death receptor regulation and celecoxib-induced apoptosis in human lung cancer cells.
2004 Dec 1
Genetic polymorphisms of human flavin monooxygenase 3 in sulindac-mediated primary chemoprevention of familial adenomatous polyposis.
2004 Dec 15
Nonsteroidal anti-inflammatory agents differ in their ability to suppress NF-kappaB activation, inhibition of expression of cyclooxygenase-2 and cyclin D1, and abrogation of tumor cell proliferation.
2004 Dec 9
The chemopreventive agent sulindac attenuates expression of the antiapoptotic protein survivin in colorectal carcinoma cells.
2004 Feb
High-dose tamoxifen and sulindac as first-line treatment for desmoid tumors.
2004 Feb 1
Induction of transcription by p21Waf1/Cip1/Sdi1: role of NFkappaB and effect of non-steroidal anti-inflammatory drugs.
2004 Jul
Integrative role of cPLA with COX-2 and the effect of non-steriodal anti-inflammatory drugs in a transgenic mouse model of amyotrophic lateral sclerosis.
2005 Apr
Delayed mechanism for induction of gamma-glutamylcysteine synthetase heavy subunit mRNA stability by oxidative stress involving p38 mitogen-activated protein kinase signaling.
2005 Aug 5
Differential gene expression of sulindac-treated human breast epithelial cells.
2005 Dec
Endothelial survival factors and spatial completion, but not pericyte coverage of retinal capillaries determine vessel plasticity.
2005 Dec
Sulindac suppresses nuclear factor-kappaB activation and RANTES gene and protein expression in endometrial stromal cells from women with endometriosis.
2005 Dec
Sulindac enhances adenoviral vector expressing mda-7/IL-24-mediated apoptosis in human lung cancer.
2005 Feb
Nonsteroidal antiinflammatory drugs differentially suppress endometriosis in a murine model.
2005 Jan
Lack of specific amyloid-beta(1-42) suppression by nonsteroidal anti-inflammatory drugs in young, plaque-free Tg2576 mice and in guinea pig neuronal cultures.
2005 Jan
Glucuronidation of nonsteroidal anti-inflammatory drugs: identifying the enzymes responsible in human liver microsomes.
2005 Jul
Sulindac enhances the proteasome inhibitor bortezomib-mediated oxidative stress and anticancer activity.
2005 Jul 15
Methylation in the p21WAF1/cip1 promoter of Apc+/-, p21+/- mice and lack of response to sulindac.
2005 Mar 17
Apoptosis of human gastric cancer SGC-7901 cells induced by mitomycin combined with sulindac.
2005 Mar 28
Sulindac induces apoptosis and protects against colon carcinoma in mice.
2005 May 14
p27kip1 in intestinal tumorigenesis and chemoprevention in the mouse.
2005 Oct 15
Sulindac activates nuclear translocation of AIF, DFF40 and endonuclease G but not induces oligonucleosomal DNA fragmentation in HT-29 cells.
2005 Sep 2
Non-steroidal anti-inflammatory drug-related hepatic damage in France and Spain: analysis from national spontaneous reporting systems.
2006 Aug
Sulindac regulates the aryl hydrocarbon receptor-mediated expression of Phase 1 metabolic enzymes in vivo and in vitro.
2006 Aug
Induction of spermidine/spermine N1-acetyltransferase (SSAT) by aspirin in Caco-2 colon cancer cells.
2006 Feb 15
Effect of the non-steroidal anti-inflammatory drug sulindac on colorectal adenomas of uncolectomized familial adenomatous polyposis.
2006 Jan
Cyclooxygenase-2 expression in hamster and human pancreatic neoplasia.
2006 Jun
Non-steroidal anti-inflammatory agents, tolmetin and sulindac, inhibit liver tryptophan 2,3-dioxygenase activity and alter brain neurotransmitter levels.
2006 Nov 10
Sulindac, a nonsteroidal anti-inflammatory drug, selectively inhibits interferon-gamma-induced expression of the chemokine CXCL9 gene in mouse macrophages.
2006 Nov 17
Inhibition of human phenol and estrogen sulfotransferase by certain non-steroidal anti-inflammatory agents.
2006 Oct
Non-steroidal anti-inflammatory agents, tolmetin and sulindac, attenuate oxidative stress in rat brain homogenate and reduce quinolinic acid-induced neurodegeneration in rat hippocampal neurons.
2006 Sep
Sulindac-derived reactive oxygen species induce apoptosis of human multiple myeloma cells via p38 mitogen activated protein kinase-induced mitochondrial dysfunction.
2007 Jan
Identification and functional analysis of common human flavin-containing monooxygenase 3 genetic variants.
2007 Jan
A phase I clinical and pharmacokinetic study of the multi-drug resistance protein-1 (MRP-1) inhibitor sulindac, in combination with epirubicin in patients with advanced cancer.
2007 Jan
Polyproline-rod approach to isolating protein targets of bioactive small molecules: isolation of a new target of indomethacin.
2007 Jan 31
Sulindac induces specific degradation of the HPV oncoprotein E7 and causes growth arrest and apoptosis in cervical carcinoma cells.
2007 Jan 8
Non-steroidal anti-inflammatory agents, tolmetin and sulindac attenuate quinolinic acid (QA)-induced oxidative stress in primary hippocampal neurons and reduce QA-induced spatial reference memory deficits in male Wistar rats.
2007 Mar 20
Patents

Sample Use Guides

CLINORIL (Sulindac) should be administered orally twice a day with food. The maximum dosage is 400 mg per day. Dosages above 400 mg per day are not recommended. In osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis, the recommended starting dosage is 150 mg twice a day. The dosage may be lowered or raised depending on the response.
Route of Administration: Oral
After 24 hours incubation with sulindac at 2mmol/L and 4mmol/L, the level of COX-2 and Bcl-2 protein were lowered in MKN45, SMMC7721 and HepG(2) cells
Substance Class Chemical
Created
by admin
on Sat Dec 17 02:19:23 UTC 2022
Edited
by admin
on Sat Dec 17 02:19:23 UTC 2022
Record UNII
184SNS8VUH
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
SULINDAC
EP   INCI   INN   JAN   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
INN   INCI   USAN  
Official Name English
SULINDAC [ORANGE BOOK]
Common Name English
ARTRIBID
Brand Name English
CLINORIL
Brand Name English
sulindac [INN]
Common Name English
SULINDAC [JAN]
Common Name English
SULINDAC [USAN]
Common Name English
1H-INDENE-3-ACETIC ACID, 5-FLUORO-2-METHYL-1-((4-(METHYLSULFINYL)PHENYL)METHYLENE)-, (1Z)-
Common Name English
ARTHROCINE
Brand Name English
SULINDAC [USP-RS]
Common Name English
SULINDAC [INCI]
Common Name English
NSC-757344
Code English
Sulindac [WHO-DD]
Common Name English
SULINDAC [MART.]
Common Name English
1H-INDENE-3-ACETIC ACID, 5-FLUORO-2-METHYL-1-((4-(METHYLSULFINYL)PHENYL)METHYLENE)-, (Z)-
Common Name English
SULINDAC [USP MONOGRAPH]
Common Name English
SULINDAC [EP MONOGRAPH]
Common Name English
SULINDAC [MI]
Common Name English
CIS-5-FLUORO-2-METHYL-1-((P-METHYLSULFINYL)BENZYLIDENE)INDENE-3-ACETIC ACID
Common Name English
MK-231
Code English
SULINDAC [VANDF]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C1323
Created by admin on Sat Dec 17 02:19:23 UTC 2022 , Edited by admin on Sat Dec 17 02:19:23 UTC 2022
WHO-ATC M01AB02
Created by admin on Sat Dec 17 02:19:23 UTC 2022 , Edited by admin on Sat Dec 17 02:19:23 UTC 2022
NDF-RT N0000175722
Created by admin on Sat Dec 17 02:19:23 UTC 2022 , Edited by admin on Sat Dec 17 02:19:23 UTC 2022
FDA ORPHAN DRUG 619917
Created by admin on Sat Dec 17 02:19:23 UTC 2022 , Edited by admin on Sat Dec 17 02:19:23 UTC 2022
LIVERTOX NBK548315
Created by admin on Sat Dec 17 02:19:23 UTC 2022 , Edited by admin on Sat Dec 17 02:19:23 UTC 2022
FDA ORPHAN DRUG 387012
Created by admin on Sat Dec 17 02:19:23 UTC 2022 , Edited by admin on Sat Dec 17 02:19:23 UTC 2022
FDA ORPHAN DRUG 818421
Created by admin on Sat Dec 17 02:19:23 UTC 2022 , Edited by admin on Sat Dec 17 02:19:23 UTC 2022
WHO-VATC QM01AB02
Created by admin on Sat Dec 17 02:19:23 UTC 2022 , Edited by admin on Sat Dec 17 02:19:23 UTC 2022
NDF-RT N0000175721
Created by admin on Sat Dec 17 02:19:23 UTC 2022 , Edited by admin on Sat Dec 17 02:19:23 UTC 2022
NDF-RT N0000000160
Created by admin on Sat Dec 17 02:19:23 UTC 2022 , Edited by admin on Sat Dec 17 02:19:23 UTC 2022
EU-Orphan Drug EU/3/12/1086
Created by admin on Sat Dec 17 02:19:23 UTC 2022 , Edited by admin on Sat Dec 17 02:19:23 UTC 2022
FDA ORPHAN DRUG 752620
Created by admin on Sat Dec 17 02:19:23 UTC 2022 , Edited by admin on Sat Dec 17 02:19:23 UTC 2022
Code System Code Type Description
CHEBI
9352
Created by admin on Sat Dec 17 02:19:23 UTC 2022 , Edited by admin on Sat Dec 17 02:19:23 UTC 2022
PRIMARY
NSC
757344
Created by admin on Sat Dec 17 02:19:23 UTC 2022 , Edited by admin on Sat Dec 17 02:19:23 UTC 2022
PRIMARY
FDA UNII
184SNS8VUH
Created by admin on Sat Dec 17 02:19:23 UTC 2022 , Edited by admin on Sat Dec 17 02:19:23 UTC 2022
PRIMARY
EVMPD
SUB10744MIG
Created by admin on Sat Dec 17 02:19:23 UTC 2022 , Edited by admin on Sat Dec 17 02:19:23 UTC 2022
PRIMARY
EPA CompTox
DTXSID4023624
Created by admin on Sat Dec 17 02:19:23 UTC 2022 , Edited by admin on Sat Dec 17 02:19:23 UTC 2022
PRIMARY
WIKIPEDIA
SULINDAC
Created by admin on Sat Dec 17 02:19:23 UTC 2022 , Edited by admin on Sat Dec 17 02:19:23 UTC 2022
PRIMARY
IUPHAR
5425
Created by admin on Sat Dec 17 02:19:23 UTC 2022 , Edited by admin on Sat Dec 17 02:19:23 UTC 2022
PRIMARY
PUBCHEM
1548887
Created by admin on Sat Dec 17 02:19:23 UTC 2022 , Edited by admin on Sat Dec 17 02:19:23 UTC 2022
PRIMARY
INN
3791
Created by admin on Sat Dec 17 02:19:23 UTC 2022 , Edited by admin on Sat Dec 17 02:19:23 UTC 2022
PRIMARY
DRUG CENTRAL
2534
Created by admin on Sat Dec 17 02:19:23 UTC 2022 , Edited by admin on Sat Dec 17 02:19:23 UTC 2022
PRIMARY
CAS
38194-50-2
Created by admin on Sat Dec 17 02:19:23 UTC 2022 , Edited by admin on Sat Dec 17 02:19:23 UTC 2022
PRIMARY
MERCK INDEX
M10382
Created by admin on Sat Dec 17 02:19:23 UTC 2022 , Edited by admin on Sat Dec 17 02:19:23 UTC 2022
PRIMARY Merck Index
NCI_THESAURUS
C850
Created by admin on Sat Dec 17 02:19:23 UTC 2022 , Edited by admin on Sat Dec 17 02:19:23 UTC 2022
PRIMARY
LACTMED
Sulindac
Created by admin on Sat Dec 17 02:19:23 UTC 2022 , Edited by admin on Sat Dec 17 02:19:23 UTC 2022
PRIMARY
DAILYMED
184SNS8VUH
Created by admin on Sat Dec 17 02:19:23 UTC 2022 , Edited by admin on Sat Dec 17 02:19:23 UTC 2022
PRIMARY
RXCUI
10237
Created by admin on Sat Dec 17 02:19:23 UTC 2022 , Edited by admin on Sat Dec 17 02:19:23 UTC 2022
PRIMARY RxNorm
ChEMBL
CHEMBL15770
Created by admin on Sat Dec 17 02:19:23 UTC 2022 , Edited by admin on Sat Dec 17 02:19:23 UTC 2022
PRIMARY
DRUG BANK
DB00605
Created by admin on Sat Dec 17 02:19:23 UTC 2022 , Edited by admin on Sat Dec 17 02:19:23 UTC 2022
PRIMARY
RS_ITEM_NUM
1642008
Created by admin on Sat Dec 17 02:19:23 UTC 2022 , Edited by admin on Sat Dec 17 02:19:23 UTC 2022
PRIMARY
ECHA (EC/EINECS)
253-819-2
Created by admin on Sat Dec 17 02:19:23 UTC 2022 , Edited by admin on Sat Dec 17 02:19:23 UTC 2022
PRIMARY
MESH
D013467
Created by admin on Sat Dec 17 02:19:23 UTC 2022 , Edited by admin on Sat Dec 17 02:19:23 UTC 2022
PRIMARY
Related Record Type Details
BINDER->LIGAND
BINDING
TRANSPORTER -> INHIBITOR
BASIS OF STRENGTH->SUBSTANCE
ASSAY (TITRATION)
EP
TRANSPORTER -> INHIBITOR
TRANSPORTER -> INHIBITOR
TRANSPORTER -> INHIBITOR
TRANSPORTER -> INHIBITOR
METABOLIC ENZYME -> SUBSTRATE
BASIS OF STRENGTH->SUBSTANCE
ASSAY (TITRATION)
USP
Related Record Type Details
METABOLITE -> PARENT
METABOLITE -> PARENT
METABOLITE ACTIVE -> PRODRUG
Available evidence indicates that the biological activity resides with the sulfide metabolite.
METABOLITE -> PARENT
METABOLITE -> PARENT
Related Record Type Details
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
Ph.Eur.; USP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
Ph.Eur.; USP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
Ph.Eur.; USP
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
CSF/PLASMA RATIO PHARMACOKINETIC