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

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	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
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	Potency
Cyclooxygenase 89	Inhibitor 8,297	0.02 µM [EC50]
Aldose reductase 44	Inhibitor 8,297	0.36 µM [IC50]
Aldo-keto reductase family 1 member B10 7	Inhibitor 8,297	2.7 µM [IC50]
transformed cell apoptotic process 108	Activator 1,430
Multidrug resistance-associated protein 4 14	Inhibitor 8,297	2.11 µM [IC50]
Canalicular multispecific organic anion transporter 1 21	Inhibitor 8,297	38.0 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Osteoarthritis 157	Primary	Approved 8,429	SULINDAC
Rheumatoid arthritis 316	Primary	Approved 8,429	SULINDAC
Ankylosing spondylitis 33	Primary	Approved 8,429	SULINDAC

C_max

Value	Dose	Co-administered	Analyte	Population
11.4 μg/mL	300 mg single, oral		SULINDAC plasma	Homo sapiens
9.21 μg/mL	400 mg single, oral		SULINDAC plasma	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
40.8 μg × h/mL	400 mg single, oral		SULINDAC plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.95 h	300 mg single, oral		SULINDAC plasma	Homo sapiens
7.8 h	200 mg single, oral		SULINDAC plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
6.9%	200 mg single, oral		SULINDAC plasma	Homo sapiens

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OAT4 146 OAT3 642 MRP4 204 OAT1 599 OAT2 145		CYP1A1 108 CYP1A2 701 CYP1B1 51

Drug as perpetrator

Show entries

Target	Modality	Activity
MRP4 238	inhibitor 3,277	yes [IC50 2.11 uM]
OAT3 644	inhibitor 3,277	yes [IC50 3.62 uM]
OAT1 603	inhibitor 3,277	yes [IC50 36.2 uM]
OAT2 147	inhibitor 3,277	yes [IC50 440 uM]
OAT4 146	inhibitor 3,277	yes [IC50 617 uM]

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Sourcing

Sourcing

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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

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PubMed

Show entries

Title	Date	PubMed
Sulindac inhibits activation of the NF-kappaB pathway.	1999 Sep 17	10480951
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
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

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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