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=CC(F)=CC=C23)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
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Description

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	Condition	Potency
transformed cell apoptotic process 104	Activator 1315
Multidrug resistance-associated protein 4 13	Inhibitor 7468		2.11 µM [IC50]
Cyclooxygenase 85	Inhibitor 7468	Spondylitis, Ankylosing	0.02 µM [EC50]
Aldose reductase 43	Inhibitor 7468		0.36 µM [IC50]
Canalicular multispecific organic anion transporter 1 19	Inhibitor 7468		38.0 µM [IC50]
Aldo-keto reductase family 1 member B10 6	Inhibitor 7468		2.7 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Osteoarthritis 148	Primary	Cyclooxygenase	Approved 7883	SULINDAC
Spondylitis, Ankylosing 9	Primary	Cyclooxygenase	Approved 7883	SULINDAC
Arthritis, Rheumatoid 146	Primary	Cyclooxygenase	Approved 7883	SULINDAC
Familial adenomatous polyposis 8			Approved (off-label) 8

PubMed

Title	Date	PubMed
Relationship of beta-catenin and Bcl-2 expression to sulindac-induced regression of intestinal tumors in Min mice.	1999 Apr	10223192
Evaluation of 5-aminosalicylic acid (5-ASA) for cancer chemoprevention: lack of efficacy against nascent adenomatous polyps in the Apc(Min) mouse.	1999 Apr	10213222
Drug-associated cholelithiasis: a case of sulindac stone formation and the incorporation of sulindac metabolites into the gallstones.	1999 Aug	10445564
Non-steroidal anti-inflammatory drugs inhibit the expression of cytokines and induce HSP70 in human monocytes.	1999 May	10328874
Non-steroidal anti-inflammatory drugs with different cyclooxygenase inhibitory profiles that prevent aberrant crypt foci formation but vary in acute gastrotoxicity in a rat model.	2000 Dec	11197048
Sulindac and a cyclooxygenase-2 inhibitor, etodolac, increase APC mRNA in the colon of rats treated with azoxymethane.	2000 Dec	11076880
Role of BAX in the apoptotic response to anticancer agents.	2000 Nov 3	11062132
Relationship between APC genotype, polyp distribution, and oral sulindac treatment in the colon and rectum of patients with familial adenomatous polyposis.	2001 Aug	11535846
Molecular analysis of sulindac-resistant adenomas in familial adenomatous polyposis.	2001 Dec	11751493
Chromatin-specific regulation of LEF-1-beta-catenin transcription activation and inhibition in vitro.	2001 Dec 15	11751639
Protein phosphatase 2A interacts with and directly dephosphorylates RelA.	2001 Dec 21	11591705
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
Regulation of renal proximal tubular epithelial cell hyaluronan generation: implications for diabetic nephropathy.	2001 May	11318944
Dysregulation of integrin-linked kinase (ILK) signaling in colonic polyposis.	2001 Sep 27	11593435
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
Discovery of molecular mechanisms of neuroprotection using cell-based bioassays and oligonucleotide arrays.	2002 Oct 29	12388792
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	12351151
Rofecoxib (Vioxx), a specific cyclooxygenase-2 inhibitor, is chemopreventive in a mouse model of colon cancer.	2003 Aug	12902858
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
Death receptor regulation and celecoxib-induced apoptosis in human lung cancer cells.	2004 Dec 1	15572759
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	15489888
Photoprotective effects of sulindac against ultraviolet B-induced phototoxicity in the skin of SKH-1 hairless mice.	2004 Mar 15	15020200
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
Sulindac suppresses nuclear factor-kappaB activation and RANTES gene and protein expression in endometrial stromal cells from women with endometriosis.	2005 Dec	16159934
Sulindac enhances adenoviral vector expressing mda-7/IL-24-mediated apoptosis in human lung cancer.	2005 Feb	15713900
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
Methylation in the p21WAF1/cip1 promoter of Apc+/-, p21+/- mice and lack of response to sulindac.	2005 Mar 17	15688007
Apoptosis of human gastric cancer SGC-7901 cells induced by mitomycin combined with sulindac.	2005 Mar 28	15793875
Non-steroidal anti-inflammatory drug-related hepatic damage in France and Spain: analysis from national spontaneous reporting systems.	2006 Aug	16867024
Inhibition of human phenol and estrogen sulfotransferase by certain non-steroidal anti-inflammatory agents.	2006 Oct	17073578
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
Polyproline-rod approach to isolating protein targets of bioactive small molecules: isolation of a new target of indomethacin.	2007 Jan 31	17243824
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

Substance Class	Chemical Created by `admin` on `Mon Oct 21 20:32:42 UTC 2019` Edited by `admin` on `Mon Oct 21 20:32:42 UTC 2019`
Record UNII	184SNS8VUH
Record Status	`Validated (UNII)`
Record Version

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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

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]

Common Name

English

SULINDAC [WHO-DD]

Common Name

English

SULINDAC [MI]

Common Name

English

CIS-5-FLUORO-2-METHYL-1-((P-METHYLSULFINYL)BENZYLIDENE)INDENE-3-ACETIC ACID

Common Name

English

SULINDAC [EP]

Common Name

English

MK-231

Code

English

SULINDAC [VANDF]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1323