SULINDAC

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 Search

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

Description
Sources: http://www.drugbank.ca/drugs/DB00605
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Cyclooxygenase 89 Target ID: CHEMBL2094253 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/017911s073lbl.pdf	Inhibitor 8228	0.02 µM [EC50]
Aldose reductase 44 Target ID: CHEMBL1900 Sources: http://www.drugbank.ca/drugs/DB00605	Inhibitor 8228	0.36 µM [IC50]
Aldo-keto reductase family 1 member B10 7 Target ID: CHEMBL5983 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25532697	Inhibitor 8228	2.7 µM [IC50]
transformed cell apoptotic process 106 Target ID: GO:0006927 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11854904	Activator 1410
Multidrug resistance-associated protein 4 14 Target ID: CHEMBL1743128 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17005917	Inhibitor 8228	2.11 µM [IC50]
Canalicular multispecific organic anion transporter 1 21 Target ID: CHEMBL5748 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17005917	Inhibitor 8228	38.0 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Osteoarthritis 157 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/017911s073lbl.pdf	Primary	Approved 8360	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
Rheumatoid arthritis 313 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/017911s073lbl.pdf	Primary	Approved 8360	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
Ankylosing spondylitis 33 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/017911s073lbl.pdf	Primary	Approved 8360	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

C_max

Value	Dose	Co-administered	Analyte	Population
11.4 μg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/8366178	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 EXPERIMENT https://ascpt.onlinelibrary.wiley.com/doi/abs/10.1038/clpt.1982.178	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

Value	Dose	Co-administered	Analyte	Population
40.8 μg × h/mL EXPERIMENT https://ascpt.onlinelibrary.wiley.com/doi/abs/10.1038/clpt.1982.178	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.95 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/8366178	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/017911s074lbl.pdf	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

F_unbound

Value	Dose	Co-administered	Analyte	Population
6.9% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/017911s074lbl.pdf	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

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OAT4 145 OAT3 636 MRP4 203 OAT1 595 OAT2 144		CYP1A1 109 CYP1A2 689 CYP1B1 52

Drug as perpetrator

Target	Modality	Activity
MRP4 237	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/17005917/	yes [IC50 2.11 uM]
OAT3 638	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/12388633/	yes [IC50 3.62 uM]
OAT1 599	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/12388633/	yes [IC50 36.2 uM]
OAT2 146	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/12388633/	yes [IC50 440 uM]
OAT4 145	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/12388633/	yes [IC50 617 uM]
CYP1A1 218	inducer 1542 Sources: https://onlinelibrary.wiley.com/doi/full/10.1002/ijc.23218	yes
CYP1A2 1673	inducer 1542 Sources: https://onlinelibrary.wiley.com/doi/full/10.1002/ijc.23218	yes
CYP1B1 68	inducer 1542 Sources: https://onlinelibrary.wiley.com/doi/full/10.1002/ijc.23218	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:9352	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:9352
ChemicalBook	CB3740374	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB3740374
MolPort	MolPort-003-666-287	https://www.molport.com/shop/molecule-link/MolPort-003-666-287
Selleck Chemicals	Sulindac(Clinoril)	http://www.selleckchem.com/products/Sulindac(Clinoril).html
eMolecules	594347	https://www.emolecules.com/cgi-bin/more?vid=594347

PubMed

Title	Date	PubMed
Growth-suppressive effect of non-steroidal anti-inflammatory drugs on 11 colon-cancer cell lines and fluorescence differential display of genes whose expression is influenced by sulindac.	2000 Dec 15	11093808
Inhibition of rat colon tumors by sulindac and sulindac sulfone is independent of K-ras (codon 12) mutation.	2000 Feb	10666051
Growth, adipose, brain, and skin alterations resulting from targeted disruption of the mouse peroxisome proliferator-activated receptor beta(delta).	2000 Jul	10866668
15-LOX-1: a novel molecular target of nonsteroidal anti-inflammatory drug-induced apoptosis in colorectal cancer cells.	2000 Jul 19	10904086
Role of BAX in the apoptotic response to anticancer agents.	2000 Nov 3	11062132
Sulindac inhibited gene expression and activity of arylamine N-acetyltransferase and DNA-2-aminofluorene adduct formation in T24 human bladder tumor cells.	2001 Dec	11828994
Enhanced apoptosis and transforming growth factor-beta1 expression in colorectal adenomas and carcinomas after Sulindac therapy.	2001 Jul	11496082
Dysregulation of integrin-linked kinase (ILK) signaling in colonic polyposis.	2001 Sep 27	11593435
Chemoprevention of esophageal adenocarcinoma by COX-2 inhibitors in an animal model of Barrett's esophagus.	2002 Apr	11910360
The influence of sulindac on patients with primary biliary cirrhosis that responds incompletely to ursodeoxycholic acid: a pilot study.	2002 Dec	12468960
New indene-derivatives with anti-proliferative properties.	2002 Feb 25	11844707
Sulindac induces apoptosis, inhibits proliferation and activates caspase-3 in Hep G2 cells.	2002 Jan-Feb	12017300
Expression and regulation of nonsteroidal anti-inflammatory drug-activated gene (NAG-1) in human and mouse tissue.	2002 May	11984525
Effects of long-term administration of sulindac on APC mRNA and apoptosis in colons of rats treated with azoxymethane.	2002 Nov	12458338
Interactions of human organic anion transporters and human organic cation transporters with nonsteroidal anti-inflammatory drugs.	2002 Nov	12388633
Novel detection and differential utilization of a c-myc transcriptional block in colon cancer chemoprevention.	2002 Nov 1	12414619
Effect of sulindac treatment for attenuated familial adenomatous polyposis with a new germline APC mutation at codon 161: report of a case.	2002 Oct	12394442
Discovery of molecular mechanisms of neuroprotection using cell-based bioassays and oligonucleotide arrays.	2002 Oct 29	12388792
A mouse model of human oral-esophageal cancer.	2002 Sep	12235107
Rofecoxib (Vioxx), a specific cyclooxygenase-2 inhibitor, is chemopreventive in a mouse model of colon cancer.	2003 Aug	12902858
Sulindac sulfide inhibits epidermal growth factor-induced phosphorylation of extracellular-regulated kinase 1/2 and Bad in human colon cancer cells.	2003 Feb 1	12566304
Cardiovascular and renal effects of cyclooxygenase inhibition in transgenic rats harboring mouse renin-2 gene (TGR[mREN2]27).	2003 Feb 14	12586211
ROCK and nuclear factor-kappaB-dependent activation of cyclooxygenase-2 by Rho GTPases: effects on tumor growth and therapeutic consequences.	2003 Jul	12857884
Regional response leading to tumorigenesis after sulindac in small and large intestine of mice with Apc mutations.	2003 Mar	12663524
Cyclooxygenase-independent induction of apoptosis by sulindac sulfone is mediated by polyamines in colon cancer.	2003 Nov 28	14506281
Prevention of retinal capillary basement membrane thickening in diabetic dogs by a non-steroidal anti-inflammatory drug.	2003 Sep	12861449
Nutritional-pharmacological combinations--a novel approach to reducing colon cancer incidence.	2004 Aug	15309441
Drug-induced liver injury.	2004 Mar 1	14986274
Sulindac suppresses nuclear factor-kappaB activation and RANTES gene and protein expression in endometrial stromal cells from women with endometriosis.	2005 Dec	16159934
Nonsteroidal antiinflammatory drugs differentially suppress endometriosis in a murine model.	2005 Jan	15652904
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	15340006
Glucuronidation of nonsteroidal anti-inflammatory drugs: identifying the enzymes responsible in human liver microsomes.	2005 Jul	15843492
Apoptosis of human gastric cancer SGC-7901 cells induced by mitomycin combined with sulindac.	2005 Mar 28	15793875
p27kip1 in intestinal tumorigenesis and chemoprevention in the mouse.	2005 Oct 15	16230399
Non-steroidal anti-inflammatory drug-related hepatic damage in France and Spain: analysis from national spontaneous reporting systems.	2006 Aug	16867024
Sulindac regulates the aryl hydrocarbon receptor-mediated expression of Phase 1 metabolic enzymes in vivo and in vitro.	2006 Aug	16531450
Sulindac, a nonsteroidal anti-inflammatory drug, selectively inhibits interferon-gamma-induced expression of the chemokine CXCL9 gene in mouse macrophages.	2006 Nov 17	17010317
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	16850258
Sulindac-derived reactive oxygen species induce apoptosis of human multiple myeloma cells via p38 mitogen activated protein kinase-induced mitochondrial dysfunction.	2007 Jan	17136320
Identification and functional analysis of common human flavin-containing monooxygenase 3 genetic variants.	2007 Jan	17050781
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	17266991

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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

Name

Type

Language

SULINDAC

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