Sulindac

Sulindac
Sulindac
Systematic (IUPAC) name
{(1Z)-5-fluoro-2-methyl-1-[4-(methylsulfinyl)benzylidene]-1H-indene-3-yl}acetic acid
Clinical data
Trade names Clinoril
AHFS/Drugs.com monograph
MedlinePlus a681037
Pregnancy cat. C(AU) C(US)
Legal status POM (UK) ℞-only (US)
Routes Oral
Pharmacokinetic data
Bioavailability Approximately 90% (Oral)
Metabolism  ?
Half-life 7.8 hours, metabolites up to 16.4 hours
Excretion Renal (50%) and fecal (25%)
Identifiers
CAS number 38194-50-2 YesY
ATC code M01AB02
PubChem CID 1548887
DrugBank APRD01243
ChemSpider 1265915 YesY
UNII 184SNS8VUH YesY
KEGG D00120 N
ChEBI CHEBI:9352 N
ChEMBL CHEMBL15770 N
Chemical data
Formula C20H17FO3S 
Mol. mass 356.412 g/mol
SMILES eMolecules & PubChem
 N(what is this?)  (verify)

Sulindac is a non-steroidal anti-inflammatory drug of the arylalkanoic acid class that is marketed in the UK & U.S. by Merck as Clinoril.

Contents

Uses

Like other NSAIDs, it is useful in the treatment of acute or chronic inflammatory conditions. Sulindac is a prodrug, derived from sulfinylindene, that is converted in the body to the active NSAID. More specifically, the agent is converted by liver enzymes to a sulfide that 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 NSAIDs except for drugs of the COX-2 inhibitor class[citation needed]. The exact mechanism of its NSAID properties is unknown, but it is thought to act on enzymes COX-1 and COX-2, inhibiting prostaglandin synthesis.

Its usual dosage is 150-200 milligrams twice per day, with food. It should not be used by persons with a history of major allergic reactions (urticaria or anaphylaxis) to aspirin or other NSAIDs, and should be used with caution by persons having pre-existing peptic ulcer disease. Sulindac is much more likely than other NSAIDs to cause damage to the liver or pancreas.

Sulindac seems to have a property, independent of COX-inhibition, of reducing the growth of polyps and precancerous lesions in the colon, especially in association with familial adenomatous polyposis, and may have other anti-cancer properties.[1][2]

Sulindac is an effective tocolytic and may be used in the treatment of preterm labor. In common with other NSAIDs, sulindac is currently being investigated for its role in the treatment of Alzheimer's disease.

Since it was found that the sulfoxide functional group can be reduced by methionine sulfoxide reductase A (MsrA), a possible anti-oxidative capability is being discussed.

Sulindac inhibits canonical Wnt signaling by blocking the PDZ Domain of the protein dishevelled.[3]

Litigation

In September 2010 a federal jury in New Hampshire awarded $21 million to a woman blinded and scarred by a generic brand of Sulindac (Clinoril) that she took for shoulder pain. Karen Bartlett said she suffered extreme burns to her skin, mucus membranes and eyes after taking sulindac.

References

  1. ^ Scheper MA, Nikitakis NG, Chaisuparat R, Montaner S, Sauk JJ (March 2007). "Sulindac induces apoptosis and inhibits tumor growth in vivo in head and neck squamous cell carcinoma". Neoplasia 9 (3): 192–9. doi:10.1593/neo.06781. PMC 1838577. PMID 17401459. http://www.neoplasia.com/abstract.php?msid=1062. 
  2. ^ Shiff SJ, Qiao L, Tsai LL, Rigas B (July 1995). "Sulindac sulfide, an aspirin-like compound, inhibits proliferation, causes cell cycle quiescence, and induces apoptosis in HT-29 colon adenocarcinoma cells". J. Clin. Invest. 96 (1): 491–503. doi:10.1172/JCI118060. PMC 185223. PMID 7615821. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=185223. 
  3. ^ Lee HJ, Wang NX, Shi DL, Zheng JJ. Sulindac Inhibits Canonical Wnt Signaling by Blocking the PDZ Domain of the Protein Dishevelled. 

External links


v · d · eNon-steroidal anti-inflammatory drug (NSAID) products (primarily M01A and M02A, also N02BA)
Salicylates
Arylalkanoic acids
2-Arylpropionic acids
(profens)
N-Arylanthranilic acids
(fenamic acids)
Pyrazolidine derivatives
Oxicams
COX-2 inhibitors
Celecoxib • Deracoxib‡ • Etoricoxib • Firocoxib‡ • Lumiracoxib† • Parecoxib • Rofecoxib† • Valdecoxib†
Sulfonanilides
Topically used products
COX-inhibiting nitric oxide donators
Others
Items listed in bold indicate initially developed compounds of specific groups. †Withdrawn drugs. ‡Veterinary use medications.
v · d · eAnti-inflammatory products (M01A)
Pyrazolidine/Butylpyrazolidines
Acetic acid derivatives
and related substances
Aceclofenac • Acemetacin • Alclofenac • Bromfenac • Bumadizone • Bufexamac • Diclofenac • Difenpiramide • Etodolac • Fentiazac • Indometacin • Ketorolac • Lonazolac • Oxametacin • Proglumetacin • Sulindac • Tolmetin • Zomepirac • Amfenac
Oxicams
Propionic acid derivatives
Fenamates
Coxibs
Other

M: MUS, DF+DRCT

anat (h/n, u, t/d, a/p, l)/phys/devp/hist

noco(m, s, c)/cong(d)/tumr, sysi/epon, injr

proc, drug (M1A/3)


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