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 8146	0.02 µM [EC50]
Aldose reductase 44 Target ID: CHEMBL1900 Sources: http://www.drugbank.ca/drugs/DB00605	Inhibitor 8146	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 8146	2.7 µM [IC50]
transformed cell apoptotic process 106 Target ID: GO:0006927 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11854904	Activator 1404
Multidrug resistance-associated protein 4 14 Target ID: CHEMBL1743128 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17005917	Inhibitor 8146	2.11 µM [IC50]
Canalicular multispecific organic anion transporter 1 21 Target ID: CHEMBL5748 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17005917	Inhibitor 8146	38.0 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Osteoarthritis 155 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/017911s073lbl.pdf	Primary	Approved 8307	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 310 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/017911s073lbl.pdf	Primary	Approved 8307	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 8307	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 625 MRP4 202 OAT1 584 OAT2 144		CYP1A1 103 CYP1A2 671 CYP1B1 50

Drug as perpetrator

Target	Modality	Activity
MRP4 235	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/17005917/	yes [IC50 2.11 uM]
OAT3 627	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/12388633/	yes [IC50 3.62 uM]
OAT1 588	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/12388633/	yes [IC50 36.2 uM]
OAT2 146	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/12388633/	yes [IC50 440 uM]
OAT4 145	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/12388633/	yes [IC50 617 uM]
CYP1A1 206	inducer 1515 Sources: https://onlinelibrary.wiley.com/doi/full/10.1002/ijc.23218	yes
CYP1A2 1620	inducer 1515 Sources: https://onlinelibrary.wiley.com/doi/full/10.1002/ijc.23218	yes
CYP1B1 66	inducer 1515 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
Drug-associated cholelithiasis: a case of sulindac stone formation and the incorporation of sulindac metabolites into the gallstones.	1999 Aug	10445564
Sulindac inhibits activation of the NF-kappaB pathway.	1999 Sep 17	10480951
Rat colorectal tumours treated with a range of non-steroidal anti-inflammatory drugs show altered cyclooxygenase-2 and cyclooxygenase-1 splice variant mRNA expression levels.	2001 Jun	11375891
Nonsteroidal anti-inflammatory drugs induce apoptosis in esophageal cancer cells by restoring 15-lipoxygenase-1 expression.	2001 Jun 15	11406566
Regulation of renal proximal tubular epithelial cell hyaluronan generation: implications for diabetic nephropathy.	2001 May	11318944
Chemoprevention of esophageal adenocarcinoma by COX-2 inhibitors in an animal model of Barrett's esophagus.	2002 Apr	11910360
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
Discovery of molecular mechanisms of neuroprotection using cell-based bioassays and oligonucleotide arrays.	2002 Oct 29	12388792
Altered expression of c-myc, p16 and p27 in rat colon tumors and its reversal by short-term treatment with chemopreventive agents.	2002 Sep	12189186
Suppression of tumorigenesis in the Apc(min) mouse: down-regulation of beta-catenin signaling by a combination of tea plus sulindac.	2003 Feb	12584176
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	12628509
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
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	12627504
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
Drug-induced liver injury.	2004 Mar 1	14986274
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	15816863
Endothelial survival factors and spatial completion, but not pericyte coverage of retinal capillaries determine vessel plasticity.	2005 Dec	16215210
Sulindac suppresses nuclear factor-kappaB activation and RANTES gene and protein expression in endometrial stromal cells from women with endometriosis.	2005 Dec	16159934
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
Sulindac enhances the proteasome inhibitor bortezomib-mediated oxidative stress and anticancer activity.	2005 Jul 15	16033843
Apoptosis of human gastric cancer SGC-7901 cells induced by mitomycin combined with sulindac.	2005 Mar 28	15793875
Sulindac induces apoptosis and protects against colon carcinoma in mice.	2005 May 14	15884131
Sulindac activates nuclear translocation of AIF, DFF40 and endonuclease G but not induces oligonucleosomal DNA fragmentation in HT-29 cells.	2005 Sep 2	15946692
Sulindac regulates the aryl hydrocarbon receptor-mediated expression of Phase 1 metabolic enzymes in vivo and in vitro.	2006 Aug	16531450
Induction of spermidine/spermine N1-acetyltransferase (SSAT) by aspirin in Caco-2 colon cancer cells.	2006 Feb 15	16262603
Cyclooxygenase-2 expression in hamster and human pancreatic neoplasia.	2006 Jun	16820089
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
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	16642371
Polyproline-rod approach to isolating protein targets of bioactive small molecules: isolation of a new target of indomethacin.	2007 Jan 31	17243824
Sulindac induces specific degradation of the HPV oncoprotein E7 and causes growth arrest and apoptosis in cervical carcinoma cells.	2007 Jan 8	16488075

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