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Details

Stereochemistry RACEMIC
Molecular Formula C20H17FO3S
Molecular Weight 356.4124
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of SULINDAC, TRANS-

SMILES

CC/1=C(CC(=O)O)c2cc(ccc2\C1=C(/[H])\c3ccc(cc3)S(=O)C)F

InChI

InChIKey=MLKXDPUZXIRXEP-RQZCQDPDSA-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 356.4124
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Description
Curator's Comment:: 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

573264000000
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

573264000000
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

573264000000
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
Sulindac inhibited gene expression and activity of arylamine N-acetyltransferase and DNA-2-aminofluorene adduct formation in T24 human bladder tumor cells.
2001 Dec
Molecular analysis of sulindac-resistant adenomas in familial adenomatous polyposis.
2001 Dec
Chromatin-specific regulation of LEF-1-beta-catenin transcription activation and inhibition in vitro.
2001 Dec 15
Protein phosphatase 2A interacts with and directly dephosphorylates RelA.
2001 Dec 21
Dysregulation of integrin-linked kinase (ILK) signaling in colonic polyposis.
2001 Sep 27
The influence of sulindac on patients with primary biliary cirrhosis that responds incompletely to ursodeoxycholic acid: a pilot study.
2002 Dec
The nonsteroidal anti-inflammatory drug sulindac causes down-regulation of signal transducer and activator of transcription 3 in human oral squamous cell carcinoma cells.
2002 Feb 15
New indene-derivatives with anti-proliferative properties.
2002 Feb 25
Induction of multidrug resistance proteins MRP1 and MRP3 and gamma-glutamylcysteine synthetase gene expression by nonsteroidal anti-inflammatory drugs in human colon cancer cells.
2002 Feb 8
Sulindac induces apoptosis, inhibits proliferation and activates caspase-3 in Hep G2 cells.
2002 Jan-Feb
Synergistic effects of (-)-epigallocatechin gallate with sulindac against colon carcinogenesis of rats treated with azoxymethane.
2002 Mar 8
Expression and regulation of nonsteroidal anti-inflammatory drug-activated gene (NAG-1) in human and mouse tissue.
2002 May
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
Rofecoxib (Vioxx), a specific cyclooxygenase-2 inhibitor, is chemopreventive in a mouse model of colon cancer.
2003 Aug
Nonsteroidal anti-inflammatory drugs inhibit growth of human neuroendocrine tumor cells via G1 cell-cycle arrest.
2003 Dec 10
Suppression of tumorigenesis in the Apc(min) mouse: down-regulation of beta-catenin signaling by a combination of tea plus sulindac.
2003 Feb
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
New TNF-alpha releasing inhibitors as cancer preventive agents from traditional herbal medicine and combination cancer prevention study with EGCG and sulindac or tamoxifen.
2003 Feb-Mar
ROCK and nuclear factor-kappaB-dependent activation of cyclooxygenase-2 by Rho GTPases: effects on tumor growth and therapeutic consequences.
2003 Jul
Regional response leading to tumorigenesis after sulindac in small and large intestine of mice with Apc mutations.
2003 Mar
Combination of tumor necrosis factor-alpha with sulindac augments its apoptotic potential and suppresses tumor growth of human carcinoma cells in nude mice.
2003 Mar 15
Hepatocellular damage from non-steroidal anti-inflammatory drugs.
2003 Nov
Cyclooxygenase-independent induction of apoptosis by sulindac sulfone is mediated by polyamines in colon cancer.
2003 Nov 28
Prevention of retinal capillary basement membrane thickening in diabetic dogs by a non-steroidal anti-inflammatory drug.
2003 Sep
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
High-dose tamoxifen and sulindac as first-line treatment for desmoid tumors.
2004 Feb 1
Drug-induced liver injury.
2004 Mar 1
Non-steroidal anti-inflammatory drug activated gene (NAG-1) expression is closely related to death receptor-4 and -5 induction, which may explain sulindac sulfide induced gastric cancer cell apoptosis.
2004 Oct
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
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
Apoptosis of human gastric cancer SGC-7901 cells induced by mitomycin combined with sulindac.
2005 Mar 28
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
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, attenuate oxidative stress in rat brain homogenate and reduce quinolinic acid-induced neurodegeneration in rat hippocampal neurons.
2006 Sep
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
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 Jun 26 08:05:46 UTC 2021
Edited
by admin
on Sat Jun 26 08:05:46 UTC 2021
Record UNII
5NVO8803F9
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
SULINDAC, TRANS-
Common Name English
SULINDAC RELATED COMPOUND A [USP-RS]
Common Name English
(E)-(5-FLUORO-2-METHYL-1-(4-(METHYLSULFINYL)BENZYLIDENE)-1H-INDEN-3-YL)ACETIC ACID
Systematic Name English
1H-INDENE-3-ACETIC ACID, 5-FLUORO-2-METHYL-1-((4-(METHYLSULFINYL)PHENYL)METHYLENE)-, (1E)-
Systematic Name English
SULINDAC RELATED COMPOUND A [USP]
Common Name English
SULINDAC, TRANS-(+/-)-
Common Name English
TRANS-SULINDAC
Common Name English
SULINDAC RELATED COMPOUND A
USP-RS  
Common Name English
SULINDAC SPECIFIED IMPURITY A [EP]
Common Name English
Code System Code Type Description
FDA UNII
5NVO8803F9
Created by admin on Sat Jun 26 08:05:46 UTC 2021 , Edited by admin on Sat Jun 26 08:05:46 UTC 2021
PRIMARY
ECHA (EC/EINECS)
258-873-0
Created by admin on Sat Jun 26 08:05:46 UTC 2021 , Edited by admin on Sat Jun 26 08:05:46 UTC 2021
PRIMARY
USP_CATALOG
1642019
Created by admin on Sat Jun 26 08:05:46 UTC 2021 , Edited by admin on Sat Jun 26 08:05:46 UTC 2021
PRIMARY USP-RS
CAS
53933-60-1
Created by admin on Sat Jun 26 08:05:46 UTC 2021 , Edited by admin on Sat Jun 26 08:05:46 UTC 2021
PRIMARY
PUBCHEM
1548885
Created by admin on Sat Jun 26 08:05:46 UTC 2021 , Edited by admin on Sat Jun 26 08:05:46 UTC 2021
PRIMARY
Related Record Type Details
ENANTIOMER -> RACEMATE
ENANTIOMER -> RACEMATE
Related Record Type Details
PARENT -> IMPURITY
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP