Indomethacin

Identification

Summary

Indomethacin is a nonsteroidal anti-inflammatory (NSAID) used for symptomatic management of chronic musculoskeletal pain conditions and to induce closure of a hemodynamically significant patent ductus arteriosus in premature infants.

Brand Names
Indocin, Tivorbex
Generic Name
Indomethacin
DrugBank Accession Number
DB00328
Background

Indometacin, or indomethacin, is a non-steroidal anti-inflammatory drug (NSAID) with anti-inflammatory, analgesic, and antipyretic properties. NSAIDs consist of agents that are structurally unrelated; the NSAID chemical classification of indometacin is an indole-acetic acid derivative with the chemical name 1- (p-chlorobenzoyl)25-methoxy-2-methylindole-3-acetic acid.1 The pharmacological effect of indometacin is not fully understood, however, it is thought to be mediated through potent and nonselective inhibition of the enzyme cyclooxygenase (COX), which is the main enzyme responsible for catalyzes the rate-limiting step in prostaglandin and thromboxane biosynthesis via the arachidonic acid (AA) pathway. Indometacin was first discovered in 1963 and it was first approved for use in the U.S. by the Food and Drug Administration in 1965, 10 along with other acetic acid derivatives such as diclofenac and sulindac that were also developed during the 1960s.1 Since then, indometacin has been extensively studied in clinical trials as one of the most potent NSAIDs in blocking prostaglandin synthesis and was among the first NSAIDs to be used in the symptomatic treatment of migraine and for headaches that eventually became known as “indomethacin-responsive” headache disorders.1

Most commonly used in rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, acute shoulder pains, and acute gouty arthritis, indometacin is currently available as oral capsules as well as other methods of administration, including rectal and intravenous formulations. Intravenous indometacin is administered to close a hemodynamically significant patent ductus arteriosus, as indicated by clinical evidence, in premature infants.14 Ophthalmic indometacin has been studied and used in the symptomatic treatment of postoperative ocular inflammation and pain and/or complications after cataract surgery. Although deemed effective in reducing ocular inflammation in clinical studies, topical NSAIDs were also associated with a potential reduction in corneal sensitivity accompanied by an increased risk of superficial punctate keratitis and subjective symptoms of discomfort, including pain, burning or pricking, or a tingling sensation after instillation into the cul‐de‐sac.6

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 357.788
Monoisotopic: 357.076785712
Chemical Formula
C19H16ClNO4
Synonyms
  • {1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}acetic acid
  • 1-(p-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetic acid
  • Indometacin
  • Indometacina
  • Indometacine
  • Indometacinum
  • Indomethacin
External IDs
  • NSC-77541

Pharmacology

Indication

Oral indometacin is indicated for symptomatic management of moderate to severe rheumatoid arthritis including acute flares of chronic disease, moderate to severe ankylosing spondylitis, moderate to severe osteoarthritis, acute painful shoulder (bursitis and/or tendinitis) and acute gouty arthritis.1,13

Intravenous indometacin is indicated to induce closure of a hemodynamically significant patent ductus arteriosus in premature infants weighing between 500 and 1750 g when after 48 hours usual medical management (e.g., fluid restriction, diuretics, digitalis, respiratory support, etc.) is ineffective.14

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Management ofAcute gouty arthritis••••••••••••
Used in combination to treatJoint painCombination Product in combination with: Levomenthol (DB00825)••• ••••••
Management ofModerate to severe osteoarthritis••••••••••••
Management ofModerate to severe rheumatoid arthritis••••••••••••
Management ofModerate to severe ankylosing spondylitis••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Indometacin is an NSAID with analgesic and antipyretic properties that exerts its pharmacological effects by inhibiting the synthesis of factors involved in pain, fever, and inflammation. Its therapeutic action does not involve pituitary-adrenal stimulation.13 Indometacin primarily works by suppressing inflammation in rheumatoid arthritis by providing relief of pain as well as reducing fever, swelling, and tenderness. This effectiveness has been demonstrated by a reduction in the extent of joint swelling, the average number of joints displaying symptoms of inflammation, and the severity of morning stiffness. Increased mobility was demonstrated by a decrease in total walking time and by improved functional capability seen as an increase in grip strength.13 In clinical trials, indometacin was shown to be effective in relieving the pain, reducing the fever, swelling, redness, and tenderness of acute gouty arthritis. Due to its pharmacological actions, the use of indometacin is associated with the risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, as well as gastrointestinal effects such as bleeding, ulceration, and perforation of the stomach or intestines.13

In a study of healthy individuals, acute oral and intravenous indometacin therapy resulted in a transiently diminished basal and CO2 stimulated cerebral blood flow; this effect disappeared in one study after one week of oral treatment.13 The clinical significance of this effect has not been established. Compared to other NSAIDs, it is suggested that indometacin is a more potent vasoconstrictor that is more consistent in decreasing cerebral blood flow and inhibiting CO2 reactivity.1 There have been studies that show indometacin directly inhibiting neuronal activity to some extent in the trigeminocervical complex after either superior salivatory nucleus or dural stimulation.1

Mechanism of action

Indometacin is a nonspecific and reversible inhibitor of the cyclo-oxygenase (COX) enzyme or prostaglandin G/H synthase. There are two identified isoforms of COX: COX-1 is universally present in most body tissues and is involved in the synthesis of the prostaglandins and thromboxane A2, while COX-2 is expressed in response to injury or inflammation.1 Constitutively expressed, the COX-1 enzyme is involved in gastric mucosal protection, platelet, and kidney function by catalyzing the conversion of arachidonic acid to prostaglandin (PG) G2 and PGG2 to PGH2.1 COX-2 is constitutively expressed and highly inducible by inflammatory stimuli. It is found in the central nervous system, kidneys, uterus, and other organs. COX-2 also catalyzes the conversion of arachidonic acid to PGG2 and PGG2 to PGH2. In the COX-2-mediated pathway, PGH2 is further converted to PGE2 and PGI2 (also known as prostacyclin). PGE2 is involved in mediating inflammation, pain, and fever. Decreasing levels of PGE2 leads to reduced inflammatory reactions. Indometacin is known to inhibit both isoforms of COX, however, with greater selectivity for COX-1, which accounts for its increased adverse gastric effects relative to other NSAIDs. It binds to the enzyme's active site and prevents the interaction between the enzyme and its substrate, arachidonic acid. Indometacin, unlike other NSAIDs, also inhibits phospholipase A2, the enzyme responsible for releasing arachidonic acid from phospholipids. The analgesic, antipyretic and anti-inflammatory effects of indomethacin as well as adverse reactions associated with the drug occur as a result of decreased prostaglandin synthesis. Its antipyretic effects may be due to action on the hypothalamus, resulting in increased peripheral blood flow, vasodilation, and subsequent heat dissipation.

The exact mechanism of action of indometacin in inducing closure of a patent ductus arteriosus is not fully understood; however, it is thought to be through inhibition of prostaglandin synthesis.13 At birth, the ductus arteriosus is normally closed as the tension of the oxygen increases significantly after birth.4 Patent ductus arteriosus in premature infants is associated with congenital heart malformations where PGE1 mediates an opposite effect to that of oxygen. PGE1 dilates the ductus arteriosus through smooth muscle relaxation and prevents the closure of the ductus arteriosus.4 By inhibiting the synthesis of prostaglandins, indometacin promotes the closure of ductus arteriosus.14

Indometacin has been described as possessing anticancer and antiviral properties through activation of protein kinase R (PKR) and downstream phosphorylation of eIF2α, inhibiting protein synthesis.11,12

TargetActionsOrganism
AProstaglandin G/H synthase 2
inhibitor
Humans
APhospholipase A2, membrane associated
inhibitor
Humans
UProstaglandin G/H synthase 1
inhibitor
Humans
UProstaglandin reductase 2
inhibitor
Humans
UPeroxisome proliferator-activated receptor gamma
activator
Humans
ULactoylglutathione lyase
inhibitor
Humans
UProstaglandin D2 receptor 2
other/unknown
Humans
UPeroxisome proliferator-activated receptor alpha
agonist
Humans
UAldo-keto reductase family 1 member C3
inhibitor
Humans
UInterferon-induced, double-stranded RNA-activated protein kinase
inducer
Humans
AHuman Cyclooxygenases
inhibitor
Humans
Absorption

Indometacin displays a linear pharmacokinetics profile where the plasma concentrations and area under the curve (AUC) are dose-proportional, whereas half-life (T1/2) and plasma and renal clearance are dose-dependent.1 Indometacin is readily and rapidly absorbed from the gastrointestinal tract. The bioavailability is virtually 100% following oral administration 1 and about 90% of the dose is absorbed within 4 hours.13 The bioavailability is about 80-90% following rectal administration.5

The peak plasma concentrations following a single oral dose were achieved between 0.9 ± 0.4 and 1.5 ± 0.8 hours in a fasting state.5 Despite large intersubject variation as well using the same preparation, peak plasma concentrations are dose-proportional and averaged 1.54 ± 0.76 μg/mL, 2.65 ± 1.03 μg/mL, and 4.92 ± 1.88 μg/mL following 25 mg, 50 mg, and 75 mg single doses in fasting subjects, respectively.5 With a typical therapeutic regimen of 25 or 50 mg t.i.d., the steady-state plasma concentrations of indomethacin are an average 1.4 times those following the first dose.13

Volume of distribution

The volume of distribution ranged from 0.34 to 1.57 L/kg following oral, intravenous, or rectal administration of single and multiple doses of indometacin in healthy individuals.7 Indometacin is distributed into the synovial fluid 2 and is extensively bound to tissues 6. It has been detected in human breast milk 2 and placenta.13 Although indometacin has been shown to cross the blood-brain barrier (BBB)13, its extensive plasma protein binding allows only the small fraction of free or unbound indometacin to diffuse across the BBB.6

Protein binding

Indometacin is a weak organic acid that is 90-99% bound to protein in plasma over the expected range of therapeutic plasma concentrations 6,13. Like other NSAIDs, indometacin is bound to plasma albumin 6 but it does not bind to red blood cells. 2

Metabolism

Indometacin undergoes hepatic metabolism involving glucuronidation, O-desmethylation, and N-deacylation.6 O-desmethyl-indomethacin, N-deschlorobenzoyl-indomethacin, and O-desmethyl-N-deschlorobenzoyl-indomethacin metabolites and their glucuronides are primarily inactive and have no pharmacological activity.6,13 Unconjugated metabolites are also detected in the plasma.13 Its high bioavailability indicates that indometacin is unlikely to be subject to the first-pass metabolism.6

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Route of elimination

Indometacin is eliminated via renal excretion, metabolism, and biliary excretion. It is also subject to enter the enterohepatic circulation through excretion of its glucuronide metabolites into bile followed by resorption of indometacin after hydrolysis 6. The extent of involvement in the enterohepatic circulation ranges from 27 to 115%.6

About 60 percent of an oral dosage is recovered in urine as drug and metabolites (26 percent as indomethacin and its glucuronide), and 33 percent in the feces (1.5 percent as indomethacin).13

Half-life

Indometacin disposition from the plasma is reported to be biphasic, with a half-life of 1 hour during the initial phase and 2.6–11.2 hours during the second phase.6 Interindividual and intraindividual variations are possible due to the extensive and sporadic nature of the enterohepatic recycling and biliary discharge of the drug.2,6

The mean half-life of oral indomethacin is estimated to be about 4.5 hours.13 The disposition of intravenous indometacin in preterm neonates was shown to vary across premature infants. In neonates older than 7 days, the mean plasma half-life of intravenous indometacin was approximately 20 hours, ranging from 15 hours in infants weighing more than 1000 g and 21 hours in infants weighing less than 1000 g.14

Clearance

In a clinical pharmacokinetic study, the plasma clearance of indometacin was reported to range from 1 to 2.5 mL/kg/min following oral administration.2

Adverse Effects
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Toxicity

Acute oral LD50 is 2.42 mg/kg in rats and 13 mg/kg in mice.MSDS The oral LD50 of indomethacin in mice and rats (based on 14-day mortality response) was 50 and 12 mg/kg, respectively.13

Symptoms of overdose may be characterized by nausea, vomiting, intense headache, dizziness, mental confusion, disorientation, or lethargy. In addition, there have been reports of paresthesias, numbness, and convulsions. In case of an overdose, the patient should receive symptomatic and supportive treatment with stomach emptying through induced vomiting or gastric lavage.13 The patient should then be closely monitored for any signs of gastrointestinal ulceration and hemorrhage. Antacids may be useful.13

Pathways
PathwayCategory
Indomethacin Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirThe metabolism of Abacavir can be decreased when combined with Indomethacin.
AbataceptThe metabolism of Indomethacin can be increased when combined with Abatacept.
AbciximabThe risk or severity of bleeding and hemorrhage can be increased when Indomethacin is combined with Abciximab.
AbrocitinibThe metabolism of Abrocitinib can be decreased when combined with Indomethacin.
AcamprosateThe excretion of Acamprosate can be decreased when combined with Indomethacin.
Food Interactions
  • Avoid alcohol. Ingestion of alcohol can increase the risk of GI bleeding.
  • Take with or without food. Food has no effect on drug absorption. However, food may decrease the extent of gastrointestinal irritation caused by indomethacin.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Indomethacin sodium0IMX38M2GG74252-25-8UHYAQBLOGVNWNT-UHFFFAOYSA-M
Product Images
International/Other Brands
Aconip (Teika Pharmaceutical Co.,Ltd.) / Arthrexin (Alphapharm) / Elmetacin (Sankyo) / Indaflex (Andromaco) / Indocid (Lundbeck) / Indolar SR (Sandoz) / Indomed (Greater Pharma) / Indoxen (Quality Pharmaceutical) / Metindol (GlaxoSmithKline) / Mikametan (Mikasa Seiyaku) / Nu-Indo (Nu-Pharm) / Reumacide (Vitória)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Indocid Cap 25mgCapsule25 mg / capOralMerck Frosst Canada & Cie, Merck Frosst Canada & Co.1965-12-311998-08-14Canada flag
Indocid Cap 50mgCapsule50 mg / capOralMerck Frosst Canada & Cie, Merck Frosst Canada & Co.1970-12-311998-08-14Canada flag
Indocid SR 75mgCapsule, extended release75 mg / capOralMerck Frosst Canada & Cie, Merck Frosst Canada & Co.1980-12-311999-08-06Canada flag
Indocid Sterile Oph Susp 1%Solution / drops10 mg / mLOphthalmicMerck Frosst Canada & Cie, Merck Frosst Canada & Co.1983-12-311999-08-06Canada flag
Indocid Sup 100mgSuppository100 mg / supRectalMerck Frosst Canada & Cie, Merck Frosst Canada & Co.1971-12-312003-08-08Canada flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Apo-indomethacinCapsule50 mgOralApotex Corporation1984-12-31Not applicableCanada flag
Apo-indomethacinCapsule25 mgOralApotex Corporation1984-12-31Not applicableCanada flag
Auro-indomethacinCapsule50 mgOralAuro Pharma Inc2021-07-08Not applicableCanada flag
Ftp-indomethacinCapsule50 mg / capOralFtp Pharmacal Inc.1998-10-092004-08-03Canada flag
Ftp-indomethacinCapsule25 mg / capOralFtp Pharmacal Inc.1998-10-092004-08-03Canada flag
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ELMETACINSpray8 mg/1mlTopicalบริษัท ดีเคเอสเอช (ประเทศไทย) จำกัด2007-10-152020-10-05Thailand flag
เอ็ม-ซินSpray8 mg/1mlTopicalบริษัท แมคโครฟาร์ จำกัด2007-04-05Not applicableThailand flag
เอลมีโก สเปรย์Spray8 mg/1mlTopicalบริษัท โรงงานผลิตเวชภัณฑ์ชินต้าเทรดดิ้ง (1971) จำกัด จำกัด1998-12-21Not applicableThailand flag
เอลเมทาซินSpray8 mg/1mlTopicalบริษัท โอลิค (ประเทศไทย) จำกัด1987-04-14Not applicableThailand flag
แวนเทลินโคว่า ครีมCream1 %w/wTopicalบริษัท โคว่า (ประเทศไทย) จำกัด2017-12-23Not applicableThailand flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
DIFMETREIndomethacin (25 mg) + Caffeine (75 mg) + Prochlorperazine maleate (2 mg)TabletViatris Italia S.R.L.2014-07-082023-10-01Italy flag
DIFMETREIndomethacin (25 mg) + Caffeine (75 mg) + Prochlorperazine maleate (2 mg)TabletMylan Italia S.R.L.2014-07-08Not applicableItaly flag
DIFMETREIndomethacin (50 mg) + Caffeine (150 mg) + Prochlorperazine maleate (8 mg)SuppositoryMylan Italia S.R.L.2014-07-08Not applicableItaly flag
DIFMETREIndomethacin (25 mg) + Caffeine (75 mg) + Prochlorperazine maleate (2 mg)TabletMylan Italia S.R.L.2014-07-08Not applicableItaly flag
DIFMETREIndomethacin (25 mg) + Caffeine (75 mg) + Prochlorperazine maleate (4 mg)SuppositoryMylan Italia S.R.L.2014-07-08Not applicableItaly flag

Categories

ATC Codes
S01CC02 — Indometacin and antiinfectivesM01AB51 — Indometacin, combinationsS01BC01 — IndometacinM02AA23 — IndometacinM01AB01 — IndometacinC01EB03 — Indometacin
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as benzoylindoles. These are organic compounds containing an indole attached to a benzoyl moiety through the acyl group.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Indoles and derivatives
Sub Class
Benzoylindoles
Direct Parent
Benzoylindoles
Alternative Parents
Indole-3-acetic acid derivatives / Indolecarboxylic acids and derivatives / 3-alkylindoles / 4-halobenzoic acids and derivatives / Anisoles / Benzoyl derivatives / Alkyl aryl ethers / Chlorobenzenes / Substituted pyrroles / Aryl chlorides
show 10 more
Substituents
3-alkylindole / 4-halobenzoic acid or derivatives / Alkyl aryl ether / Anisole / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Benzenoid / Benzoic acid or derivatives
show 27 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
aromatic ether, monochlorobenzenes, N-acylindole, indole-3-acetic acids (CHEBI:49662) / a small molecule (CPD-10545)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
XXE1CET956
CAS number
53-86-1
InChI Key
CGIGDMFJXJATDK-UHFFFAOYSA-N
InChI
InChI=1S/C19H16ClNO4/c1-11-15(10-18(22)23)16-9-14(25-2)7-8-17(16)21(11)19(24)12-3-5-13(20)6-4-12/h3-9H,10H2,1-2H3,(H,22,23)
IUPAC Name
2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetic acid
SMILES
COC1=CC2=C(C=C1)N(C(=O)C1=CC=C(Cl)C=C1)C(C)=C2CC(O)=O

References

Synthesis Reference

Hubertus L. Regtop, John R. Biffin, "Preparation of divalent metal salts of indomethacin." U.S. Patent US5310936, issued November, 1917.

US5310936
General References
  1. Lucas S: The Pharmacology of Indomethacin. Headache. 2016 Feb;56(2):436-46. doi: 10.1111/head.12769. Epub 2016 Feb 11. [Article]
  2. Helleberg L: Clinical Pharmacokinetics of indomethacin. Clin Pharmacokinet. 1981 Jul-Aug;6(4):245-58. doi: 10.2165/00003088-198106040-00001. [Article]
  3. Nalamachu S, Wortmann R: Role of indomethacin in acute pain and inflammation management: a review of the literature. Postgrad Med. 2014 Jul;126(4):92-7. doi: 10.3810/pgm.2014.07.2787. [Article]
  4. Pacifici GM: Clinical pharmacology of indomethacin in preterm infants: implications in patent ductus arteriosus closure. Paediatr Drugs. 2013 Oct;15(5):363-76. doi: 10.1007/s40272-013-0031-7. [Article]
  5. Jensen KM, Grenabo L: Bioavailability of indomethacin after intramuscular injection and rectal administration of solution and suppositories. Acta Pharmacol Toxicol (Copenh). 1985 Nov;57(5):322-7. [Article]
  6. Weber M, Kodjikian L, Kruse FE, Zagorski Z, Allaire CM: Efficacy and safety of indomethacin 0.1% eye drops compared with ketorolac 0.5% eye drops in the management of ocular inflammation after cataract surgery. Acta Ophthalmol. 2013 Feb;91(1):e15-21. doi: 10.1111/j.1755-3768.2012.02520.x. Epub 2012 Sep 12. [Article]
  7. Alvan G, Orme M, Bertilsson L, Ekstrand R, Palmer L: Pharmacokinetics of indomethacin. Clin Pharmacol Ther. 1975 Sep;18(3):364-73. [Article]
  8. Ricciotti E, FitzGerald GA: Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol. 2011 May;31(5):986-1000. doi: 10.1161/ATVBAHA.110.207449. [Article]
  9. Rouzer CA, Marnett LJ: Cyclooxygenases: structural and functional insights. J Lipid Res. 2009 Apr;50 Suppl:S29-34. doi: 10.1194/jlr.R800042-JLR200. Epub 2008 Oct 23. [Article]
  10. HART FD, BOARDMAN PL: INDOMETHACIN: A NEW NON-STEROID ANTI-INFLAMMATORY AGENT. Br Med J. 1963 Oct 19;2(5363):965-70. [Article]
  11. Brunelli C, Amici C, Angelini M, Fracassi C, Belardo G, Santoro MG: The non-steroidal anti-inflammatory drug indomethacin activates the eIF2alpha kinase PKR, causing a translational block in human colorectal cancer cells. Biochem J. 2012 Apr 15;443(2):379-86. doi: 10.1042/BJ20111236. [Article]
  12. Amici C, La Frazia S, Brunelli C, Balsamo M, Angelini M, Santoro MG: Inhibition of viral protein translation by indomethacin in vesicular stomatitis virus infection: role of eIF2alpha kinase PKR. Cell Microbiol. 2015 Sep;17(9):1391-404. doi: 10.1111/cmi.12446. Epub 2015 May 13. [Article]
  13. Indomethacin Capsules (25 mg) - FDA Label [Link]
  14. Indocin I.V. (indomethacin for injection) - FDA Label [Link]
  15. FDA Approved Drug Products: INDOCIN (indomethacin) Suppositories, for rectal use [Link]
Human Metabolome Database
HMDB0014473
KEGG Drug
D00141
KEGG Compound
C01926
PubChem Compound
3715
PubChem Substance
46508291
ChemSpider
3584
BindingDB
17638
RxNav
5781
ChEBI
49662
ChEMBL
CHEMBL6
ZINC
ZINC000000601283
Therapeutic Targets Database
DAP000617
PharmGKB
PA449982
Guide to Pharmacology
GtP Drug Page
PDBe Ligand
IMN
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Indometacin
PDB Entries
1s2a / 1z9h / 2bxk / 2bxm / 2bxq / 2dm6 / 2oth / 2zb8 / 3ads / 3adx
show 14 more
MSDS
Download (73.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedBasic ScienceHealthy, Male / Neuromuscular Function2
4CompletedPreventionAcute Pancreatitis1
4CompletedPreventionCataracts / Inflammation1
4CompletedPreventionFamily Planning1
4CompletedPreventionHealthy Volunteers (HV)1

Pharmacoeconomics

Manufacturers
  • Iroko pharmaceuticals llc
  • Sandoz inc
  • Able laboratories inc
  • Avanthi inc
  • Inwood laboratories inc sub forest laboratories inc
  • Teva pharmaceuticals usa inc
  • Duramed pharmaceuticals inc sub barr laboratories inc
  • Halsey drug co inc
  • Heritage pharmaceuticals inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Mutual pharmaceutical co inc
  • Mylan pharmaceuticals inc
  • Parke davis div warner lambert co
  • Pioneer pharmaceuticals inc
  • Pliva inc
  • Roxane laboratories inc
  • Superpharm corp
  • Vintage pharmaceuticals llc
  • Watson laboratories inc
  • App pharmaceuticals llc
  • G and w laboratories inc
  • Lundbeck inc
  • Bedford laboratories div ben venue laboratories inc
Packagers
  • Advanced Pharmaceutical Services Inc.
  • Amerisource Health Services Corp.
  • Apotheca Inc.
  • Apothecary Shop Wholesale
  • A-S Medication Solutions LLC
  • Bedford Labs
  • Bryant Ranch Prepack
  • Cardinal Health
  • Caremark LLC
  • Central Texas Community Health Centers
  • Comprehensive Consultant Services Inc.
  • DHHS Program Support Center Supply Service Center
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Emcure Pharmaceuticals Ltd.
  • Endo Pharmaceuticals Inc.
  • Eon Labs
  • G & W Labs
  • Group Health Cooperative
  • H.J. Harkins Co. Inc.
  • Heartland Repack Services LLC
  • Inwood Labs
  • Iroko Pharmaceuticals
  • Kaiser Foundation Hospital
  • KVK-Tech Inc.
  • Lake Erie Medical and Surgical Supply
  • Liberty Pharmaceuticals
  • Lundbeck Inc.
  • Major Pharmaceuticals
  • Medisca Inc.
  • Medvantx Inc.
  • Merck & Co.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Novopharm Ltd.
  • Nucare Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • Patient First Corp.
  • PCA LLC
  • PD-Rx Pharmaceuticals Inc.
  • Pharmedix
  • Physicians Total Care Inc.
  • Pliva Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepackage Specialists
  • Prescription Dispensing Service Inc.
  • Qualitest
  • Rebel Distributors Corp.
  • Redpharm Drug
  • Remedy Repack
  • Sandhills Packaging Inc.
  • Sandoz
  • Southwood Pharmaceuticals
  • St Mary's Medical Park Pharmacy
  • Talbert Medical Management Corp.
  • Teva Pharmaceutical Industries Ltd.
  • Tya Pharmaceuticals
  • UDL Laboratories
  • United Research Laboratories Inc.
  • Veratex Corp.
Dosage Forms
FormRouteStrength
CapsuleOral60.0000 mg
CapsuleOral
Suppository
Tablet
CapsuleOral25.000 mg
Capsule, coated pelletsOral75 mg
CapsuleOral25.00 MG
CreamCutaneous2.500 g
Capsule, extended releaseOral75 MG
Solution / dropsOphthalmic
SuppositoryRectal100.000 mg
CapsuleOral
CapsuleOral25 mg / cap
Capsule, extended releaseOral75 mg / cap
Solution / dropsOphthalmic10 mg / mL
Injection, powder, lyophilized, for solutionIntravenous1 mg
Injection, powder, lyophilized, for solutionIntravenous1 mg/1
SuppositoryRectal50 mg/1
SuspensionOral25 mg/5mL
Solution / dropsOphthalmic0.1 %
Solution / dropsOphthalmic1 MG/ML
Liquid; powder, for solutionOphthalmic1 mg / 1 mL
Solution / dropsOphthalmic
Solution / dropsOphthalmic5 MG/ML
CapsuleOral25 mg/1
CapsuleOral50 mg/1
Capsule, extended releaseOral75 mg/1
Injection, powder, for solutionIntravenous0.1 mg/0.1mL
Injection, powder, lyophilized, for solutionIntravenous1 mg/1mL
CapsuleOral75 mg/1
Capsule, coated pelletsOral
Injection, powder, for solutionIntravenous; Parenteral25 MG/2ML
Injection, powder, for solutionIntravenous; Parenteral50 MG/2ML
Capsule, extended releaseOral
SuppositoryRectal
SolutionIntravenous1.00 mg
SolutionTopical
GelCutaneous
Capsule, liquid filledOral25 mg
SuppositoryRectal100 mg / sup
SuppositoryRectal50 mg / sup
SuppositoryRectal100 mg
SuppositoryRectal50 mg
CapsuleOral50 mg / cap
TabletOral
GelCutaneous500.000 mg
GelTopical
CapsuleOral20 mg/1
CapsuleOral40 mg/1
Capsule
CapsuleOral25 mg
Tablet25 mg
Tablet, sugar coatedOral25 mg
Tablet, film coated25 mg
Tablet, film coated50 mg
CapsuleOral50 mg
Tablet, coatedOral25 mg
SprayTopical8 mg/1ml
CreamTopical1 %w/w
Prices
Unit descriptionCostUnit
Indocin i.v. 1 mg vial642.6USD vial
Indomethacin 1 mg vial600.0USD vial
Indocin 50 mg suppository9.56USD suppository
Indomethacin CR 75 mg capsule3.12USD capsule
Indocin sr 75 mg capsule2.92USD capsule
Indomethacin powder2.57USD g
Ratio-Indomethacin 100 mg Suppository0.93USD suppository
Sandoz Indomethacin 100 mg Suppository0.93USD suppository
Sandoz Indomethacin 50 mg Suppository0.93USD suppository
Indomethacin 50 mg capsule0.65USD capsule
Indomethacin 25 mg capsule0.44USD capsule
Apo-Indomethacin 50 mg Capsule0.16USD capsule
Novo-Methacin 50 mg Capsule0.16USD capsule
Nu-Indo 50 mg Capsule0.16USD capsule
Apo-Indomethacin 25 mg Capsule0.09USD capsule
Novo-Methacin 25 mg Capsule0.09USD capsule
Nu-Indo 25 mg Capsule0.09USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US9089471No2015-07-282030-04-23US flag
US8992982No2015-03-312030-04-23US flag
US8734847No2014-05-272030-04-23US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)151U.S. Patent 3,161,654.
water solubility0.937 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP4.27HANSCH,C ET AL. (1995)
logS-4.62ADME Research, USCD
Caco2 permeability-4.69ADME Research, USCD
pKa4.5BUDAVARI,S ET AL. (1989)
Predicted Properties
PropertyValueSource
Water Solubility0.0024 mg/mLALOGPS
logP4.25ALOGPS
logP3.53Chemaxon
logS-5.2ALOGPS
pKa (Strongest Acidic)3.79Chemaxon
pKa (Strongest Basic)-2.9Chemaxon
Physiological Charge-1Chemaxon
Hydrogen Acceptor Count4Chemaxon
Hydrogen Donor Count1Chemaxon
Polar Surface Area68.53 Å2Chemaxon
Rotatable Bond Count4Chemaxon
Refractivity94.81 m3·mol-1Chemaxon
Polarizability36.64 Å3Chemaxon
Number of Rings3Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9509
Blood Brain Barrier+0.9381
Caco-2 permeable+0.5857
P-glycoprotein substrateNon-substrate0.636
P-glycoprotein inhibitor INon-inhibitor0.9313
P-glycoprotein inhibitor IINon-inhibitor0.834
Renal organic cation transporterNon-inhibitor0.8334
CYP450 2C9 substrateNon-substrate0.712
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.6436
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9302
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6978
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.8728
BiodegradationNot ready biodegradable0.9743
Rat acute toxicity4.0722 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9818
hERG inhibition (predictor II)Non-inhibitor0.8306
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (7.7 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-000i-0921000000-71472b2fb43c8acb2e55
GC-MS Spectrum - EI-BGC-MSsplash10-002f-9100000000-2545b33ef519ca9557d7
Mass Spectrum (Electron Ionization)MSsplash10-000i-1901000000-710010c41f0ded9b0f17
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-000i-2902000000-8effecdaf737eb86e781
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-000i-0901000000-aa0cdbd9e10c432d837c
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-014u-2900000000-3bf048feb0cc9b0867e8
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-03di-0009000000-5a4abda1542473813a5d
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-03di-0019000000-b80206e17a22fdf15299
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0002-0093000000-4e04725a4a7ea8db1880
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0bt9-0906000000-44825d096b6f8c6091ab
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-053r-0890000000-e9f8e33084842b2a91e0
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0a4i-0900000000-5aee2869a858e70aa8cb
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0a4i-0900000000-5aee2869a858e70aa8cb
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-03di-0019000000-b9916635c4db449698ab
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0002-0092000000-270cd44f32c881ded6aa
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0a4j-0973000000-6e9ac766080e35c8b297
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-053r-0790000000-b0e6139fc1746c17ddb7
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0a4i-0900000000-1df95eb7ff5058a870cc
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-03di-0009000000-6a65e96ca253d6a3dda0
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-08gi-0195000000-7ea82149ddaa783e01df
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-00di-0900000000-1208c0d5e605b8b69605
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4r-0709000000-1814b324e15b59fa31a5
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-000i-0900000000-da84cf2df3db68610ae6
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-000i-0900000000-f05d502a85960fefa1b3
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-000i-0900000000-ef4bc1155685673e5c96
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-000i-1900000000-f3d47b27b5deef302e24
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-000i-1900000000-529c521348d72ac3ac2c
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4r-0709000000-552147af435f6203b275
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-000i-0900000000-3ecb36f2b39a0a31490e
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-000i-0900000000-3f989b1435664e5bd1c9
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-000i-0900000000-432dc50c7beda844e96f
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-000i-0900000000-3a2c27afaa406477bb36
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-000i-1900000000-30707a04c6d14ccc1494
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-00di-0900000000-ceb3b04d9de59607c950
MS/MS Spectrum - , positiveLC-MS/MSsplash10-000i-2902000000-8effecdaf737eb86e781
MS/MS Spectrum - , positiveLC-MS/MSsplash10-000i-0901000000-aa0cdbd9e10c432d837c
MS/MS Spectrum - , positiveLC-MS/MSsplash10-000i-3900000000-353e94b605ae82792fae
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-000i-0901000000-5c9675c7c76c033ffc5b
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-0009000000-7a21f3ce0463915fd604
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4i-0009000000-aa85475b506e40224aaf
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4r-0839000000-de3bcfe4027e9454d01f
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-053r-8029000000-769e2411f9d152f46d93
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-052r-0910000000-91e7cbb2a0c96149d304
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-001i-9010000000-5177a0b85e9459459e27
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-0009000000-7a21f3ce0463915fd604
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4i-0009000000-aa85475b506e40224aaf
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4r-0839000000-de3bcfe4027e9454d01f
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-053r-8029000000-769e2411f9d152f46d93
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-052r-0910000000-91e7cbb2a0c96149d304
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-001i-9010000000-5177a0b85e9459459e27
1H NMR Spectrum1D NMRNot Applicable
13C NMR Spectrum1D NMRNot Applicable
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-191.8318517
predicted
DarkChem Lite v0.1.0
[M-H]-192.3842517
predicted
DarkChem Lite v0.1.0
[M-H]-192.0699517
predicted
DarkChem Lite v0.1.0
[M-H]-181.18584
predicted
DeepCCS 1.0 (2019)
[M-H]-191.8318517
predicted
DarkChem Lite v0.1.0
[M-H]-192.3842517
predicted
DarkChem Lite v0.1.0
[M-H]-192.0699517
predicted
DarkChem Lite v0.1.0
[M-H]-181.18584
predicted
DeepCCS 1.0 (2019)
[M+H]+192.2708517
predicted
DarkChem Lite v0.1.0
[M+H]+193.6368517
predicted
DarkChem Lite v0.1.0
[M+H]+192.5201517
predicted
DarkChem Lite v0.1.0
[M+H]+183.56938
predicted
DeepCCS 1.0 (2019)
[M+H]+192.2708517
predicted
DarkChem Lite v0.1.0
[M+H]+193.6368517
predicted
DarkChem Lite v0.1.0
[M+H]+192.5201517
predicted
DarkChem Lite v0.1.0
[M+H]+183.56938
predicted
DeepCCS 1.0 (2019)
[M+Na]+192.1285517
predicted
DarkChem Lite v0.1.0
[M+Na]+193.4278517
predicted
DarkChem Lite v0.1.0
[M+Na]+192.0808517
predicted
DarkChem Lite v0.1.0
[M+Na]+191.20998
predicted
DeepCCS 1.0 (2019)
[M+Na]+192.1285517
predicted
DarkChem Lite v0.1.0
[M+Na]+193.4278517
predicted
DarkChem Lite v0.1.0
[M+Na]+192.0808517
predicted
DarkChem Lite v0.1.0
[M+Na]+191.20998
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
Curator comments
IC50 = 0.48 microM
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and...
Gene Name
PTGS2
Uniprot ID
P35354
Uniprot Name
Prostaglandin G/H synthase 2
Molecular Weight
68995.625 Da
References
  1. Armstrong PJ, Franklin DP, Carey DJ, Elmore JR: Suppression of experimental aortic aneurysms: comparison of inducible nitric oxide synthase and cyclooxygenase inhibitors. Ann Vasc Surg. 2005 Mar;19(2):248-57. [Article]
  2. Jerde TJ, Calamon-Dixon JL, Bjorling DE, Nakada SY: Celecoxib inhibits ureteral contractility and prostanoid release. Urology. 2005 Jan;65(1):185-90. [Article]
  3. Pilane CM, Labelle EF: Nitric oxide stimulated vascular smooth muscle cells undergo apoptosis induced in part by arachidonic acid derived eicosanoids. J Cell Physiol. 2005 Aug;204(2):423-7. [Article]
  4. Yokota A, Taniguchi M, Takahira Y, Tanaka A, Takeuchi K: Rofecoxib produces intestinal but not gastric damage in the presence of a low dose of indomethacin in rats. J Pharmacol Exp Ther. 2005 Jul;314(1):302-9. Epub 2005 Apr 14. [Article]
  5. Zhang GS, Fu YB, Xia M: [Proliferation inhibition effect of indomethacin on CML cells associated with down-regulation of phosphorylated STAT1/STAT5 and inhibition of COX-2 expression]. Zhonghua Xue Ye Xue Za Zhi. 2004 Dec;25(12):732-5. [Article]
  6. Blanco FJ, Guitian R, Moreno J, de Toro FJ, Galdo F: Effect of antiinflammatory drugs on COX-1 and COX-2 activity in human articular chondrocytes. J Rheumatol. 1999 Jun;26(6):1366-73. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Phospholipid binding
Specific Function
Thought to participate in the regulation of the phospholipid metabolism in biomembranes including eicosanoid biosynthesis. Catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-ph...
Gene Name
PLA2G2A
Uniprot ID
P14555
Uniprot Name
Phospholipase A2, membrane associated
Molecular Weight
16082.525 Da
References
  1. Geisslinger, G., & Lötsch, J. (2004). Non-steroidal anti-inflammatory drugs. In Encyclopedic reference of molecular pharmacology (pp. 667-671). Berlin: Springer. [ISBN:9783540298328]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
IC50 = 0.063 microM
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gas...
Gene Name
PTGS1
Uniprot ID
P23219
Uniprot Name
Prostaglandin G/H synthase 1
Molecular Weight
68685.82 Da
References
  1. Bobadilla L RA, Perez-Alvarez V, Bracho Valdes I, Lopez-Sanchez P: Effect of pregnancy on the roles of nitric oxide and prostaglandins in 5-hydroxytryptamine-induced contractions in rat isolated thoracic and abdominal aorta. Clin Exp Pharmacol Physiol. 2005 Mar;32(3):202-9. [Article]
  2. Fornai M, Blandizzi C, Colucci R, Antonioli L, Bernardini N, Segnani C, Baragatti B, Barogi S, Berti P, Spisni R, Del Tacca M: Role of cyclooxygenases 1 and 2 in the modulation of neuromuscular functions in the distal colon of humans and mice. Gut. 2005 May;54(5):608-16. [Article]
  3. Higuchi K, Tominaga K, Watanabe T, Uno H, Shiba M, Sasaki E, Tanigawa T, Takashima T, Hamaguchi M, Oshitani N, Matsumoto T, Iwanaga Y, Fukuda T, Fujiwara Y, Arakawa T: Indomethacin, but not Helicobacter pylori, inhibits adaptive relaxation in isolated guinea-pig stomach. Drugs Exp Clin Res. 2004;30(5-6):235-41. [Article]
  4. Kundu N, Walser TC, Ma X, Fulton AM: Cyclooxygenase inhibitors modulate NK activities that control metastatic disease. Cancer Immunol Immunother. 2005 Oct;54(10):981-7. Epub 2005 May 13. [Article]
  5. Moth CW, Prusakiewicz JJ, Marnett LJ, Lybrand TP: Stereoselective binding of indomethacin ethanolamide derivatives to cyclooxygenase-1. J Med Chem. 2005 May 19;48(10):3613-20. [Article]
  6. Blanco FJ, Guitian R, Moreno J, de Toro FJ, Galdo F: Effect of antiinflammatory drugs on COX-1 and COX-2 activity in human articular chondrocytes. J Rheumatol. 1999 Jun;26(6):1366-73. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
15-oxoprostaglandin 13-oxidase activity
Specific Function
Functions as 15-oxo-prostaglandin 13-reductase and acts on 15-keto-PGE1, 15-keto-PGE2, 15-keto-PGE1-alpha and 15-keto-PGE2-alpha with highest activity towards 15-keto-PGE2. Overexpression represses...
Gene Name
PTGR2
Uniprot ID
Q8N8N7
Uniprot Name
Prostaglandin reductase 2
Molecular Weight
38498.74 Da
References
  1. Wu YH, Ko TP, Guo RT, Hu SM, Chuang LM, Wang AH: Structural basis for catalytic and inhibitory mechanisms of human prostaglandin reductase PTGR2. Structure. 2008 Nov 12;16(11):1714-23. doi: 10.1016/j.str.2008.09.007. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Activator
General Function
Zinc ion binding
Specific Function
Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE...
Gene Name
PPARG
Uniprot ID
P37231
Uniprot Name
Peroxisome proliferator-activated receptor gamma
Molecular Weight
57619.58 Da
References
  1. Cho MC, Lee HS, Kim JH, Choe YK, Hong JT, Paik SG, Yoon DY: A simple ELISA for screening ligands of peroxisome proliferator-activated receptor-gamma. J Biochem Mol Biol. 2003 Mar 31;36(2):207-13. [Article]
  2. Lehmann JM, Lenhard JM, Oliver BB, Ringold GM, Kliewer SA: Peroxisome proliferator-activated receptors alpha and gamma are activated by indomethacin and other non-steroidal anti-inflammatory drugs. J Biol Chem. 1997 Feb 7;272(6):3406-10. [Article]
Details
6. Lactoylglutathione lyase
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Catalyzes the conversion of hemimercaptal, formed from methylglyoxal and glutathione, to S-lactoylglutathione. Involved in the regulation of TNF-induced transcriptional activity of NF-kappa-B. Requ...
Gene Name
GLO1
Uniprot ID
Q04760
Uniprot Name
Lactoylglutathione lyase
Molecular Weight
20777.515 Da
References
  1. Sato S, Kwon Y, Kamisuki S, Srivastava N, Mao Q, Kawazoe Y, Uesugi M: Polyproline-rod approach to isolating protein targets of bioactive small molecules: isolation of a new target of indomethacin. J Am Chem Soc. 2007 Jan 31;129(4):873-80. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Other/unknown
General Function
Prostaglandin j receptor activity
Specific Function
Receptor for prostaglandin D2 (PGD2). Coupled to the G(i)-protein. Receptor activation may result in pertussis toxin-sensitive decreases in cAMP levels and Ca(2+) mobilization. PI3K signaling is al...
Gene Name
PTGDR2
Uniprot ID
Q9Y5Y4
Uniprot Name
Prostaglandin D2 receptor 2
Molecular Weight
43267.15 Da
References
  1. Hata AN, Lybrand TP, Breyer RM: Identification of determinants of ligand binding affinity and selectivity in the prostaglandin D2 receptor CRTH2. J Biol Chem. 2005 Sep 16;280(37):32442-51. Epub 2005 Jul 19. [Article]
  2. Hata AN, Lybrand TP, Marnett LJ, Breyer RM: Structural determinants of arylacetic acid nonsteroidal anti-inflammatory drugs necessary for binding and activation of the prostaglandin D2 receptor CRTH2. Mol Pharmacol. 2005 Mar;67(3):640-7. Epub 2004 Nov 24. [Article]
  3. Mathiesen JM, Ulven T, Martini L, Gerlach LO, Heinemann A, Kostenis E: Identification of indole derivatives exclusively interfering with a G protein-independent signaling pathway of the prostaglandin D2 receptor CRTH2. Mol Pharmacol. 2005 Aug;68(2):393-402. Epub 2005 May 3. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleyleth...
Gene Name
PPARA
Uniprot ID
Q07869
Uniprot Name
Peroxisome proliferator-activated receptor alpha
Molecular Weight
52224.595 Da
References
  1. Lehmann JM, Lenhard JM, Oliver BB, Ringold GM, Kliewer SA: Peroxisome proliferator-activated receptors alpha and gamma are activated by indomethacin and other non-steroidal anti-inflammatory drugs. J Biol Chem. 1997 Feb 7;272(6):3406-10. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity
Specific Function
Catalyzes the conversion of aldehydes and ketones to alcohols. Catalyzes the reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ) and the oxidation of 9-alpha,11-beta-PGF2 to PGD2....
Gene Name
AKR1C3
Uniprot ID
P42330
Uniprot Name
Aldo-keto reductase family 1 member C3
Molecular Weight
36852.89 Da
References
  1. Lovering AL, Ride JP, Bunce CM, Desmond JC, Cummings SM, White SA: Crystal structures of prostaglandin D(2) 11-ketoreductase (AKR1C3) in complex with the nonsteroidal anti-inflammatory drugs flufenamic acid and indomethacin. Cancer Res. 2004 Mar 1;64(5):1802-10. [Article]
  2. Adeniji A, Uddin MJ, Zang T, Tamae D, Wangtrakuldee P, Marnett LJ, Penning TM: Discovery of (R)-2-(6-Methoxynaphthalen-2-yl)butanoic Acid as a Potent and Selective Aldo-keto Reductase 1C3 Inhibitor. J Med Chem. 2016 Aug 25;59(16):7431-44. doi: 10.1021/acs.jmedchem.6b00160. Epub 2016 Aug 12. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
IFN-induced dsRNA-dependent serine/threonine-protein kinase which plays a key role in the innate immune response to viral infection and is also involved in the regulation of signal transduction, apoptosis, cell proliferation and differentiation. Exerts its antiviral activity on a wide range of DNA and RNA viruses including hepatitis C virus (HCV), hepatitis B virus (HBV), measles virus (MV) and herpes simplex virus 1 (HHV-1). Inhibits viral replication via phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (EIF2S1), this phosphorylation impairs the recycling of EIF2S1 between successive rounds of initiation leading to inhibition of translation which eventually results in shutdown of cellular and viral protein synthesis. Also phosphorylates other substrates including p53/TP53, PPP2R5A, DHX9, ILF3, IRS1 and the HHV-1 viral protein US11. In addition to serine/threonine-protein kinase activity, also has tyrosine-protein kinase activity and phosphorylates CDK1 at 'Tyr-4' upon DNA damage, facilitating its ubiquitination and proteosomal degradation. Either as an adapter protein and/or via its kinase activity, can regulate various signaling pathways (p38 MAP kinase, NF-kappa-B and insulin signaling pathways) and transcription factors (JUN, STAT1, STAT3, IRF1, ATF3) involved in the expression of genes encoding proinflammatory cytokines and IFNs. Activates the NF-kappa-B pathway via interaction with IKBKB and TRAF family of proteins and activates the p38 MAP kinase pathway via interaction with MAP2K6. Can act as both a positive and negative regulator of the insulin signaling pathway (ISP). Negatively regulates ISP by inducing the inhibitory phosphorylation of insulin receptor substrate 1 (IRS1) at 'Ser-312' and positively regulates ISP via phosphorylation of PPP2R5A which activates FOXO1, which in turn up-regulates the expression of insulin receptor substrate 2 (IRS2). Can regulate NLRP3 inflammasome assembly and the activation of NLRP3, NLRP1, AIM2 and NLRC4 inflammasomes. Can trigger apoptosis via FADD-mediated activation of CASP8. Plays a role in the regulation of the cytoskeleton by binding to gelsolin (GSN), sequestering the protein in an inactive conformation away from actin.
Specific Function
Atp binding
Gene Name
EIF2AK2
Uniprot ID
P19525
Uniprot Name
Interferon-induced, double-stranded RNA-activated protein kinase
Molecular Weight
62093.71 Da
References
  1. Brunelli C, Amici C, Angelini M, Fracassi C, Belardo G, Santoro MG: The non-steroidal anti-inflammatory drug indomethacin activates the eIF2alpha kinase PKR, causing a translational block in human colorectal cancer cells. Biochem J. 2012 Apr 15;443(2):379-86. doi: 10.1042/BJ20111236. [Article]
  2. Amici C, La Frazia S, Brunelli C, Balsamo M, Angelini M, Santoro MG: Inhibition of viral protein translation by indomethacin in vesicular stomatitis virus infection: role of eIF2alpha kinase PKR. Cell Microbiol. 2015 Sep;17(9):1391-404. doi: 10.1111/cmi.12446. Epub 2015 May 13. [Article]
Kind
Protein group
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gas...

Components:
References
  1. Raddino R, Pela G, Manca C, Barbagallo M, D'Aloia A, Passeri M, Visioli O: Mechanism of action of human calcitonin gene-related peptide in rabbit heart and in human mammary arteries. J Cardiovasc Pharmacol. 1997 Apr;29(4):463-70. doi: 10.1097/00005344-199704000-00006. [Article]
  2. Camras CB, Miranda OC: The putative role of prostaglandins in surgical miosis. Prog Clin Biol Res. 1989;312:197-210. [Article]
  3. Usami M, Kishimoto K, Ohata A, Miyoshi M, Aoyama M, Fueda Y, Kotani J: Butyrate and trichostatin A attenuate nuclear factor kappaB activation and tumor necrosis factor alpha secretion and increase prostaglandin E2 secretion in human peripheral blood mononuclear cells. Nutr Res. 2008 May;28(5):321-8. doi: 10.1016/j.nutres.2008.02.012. [Article]
  4. Emerit I, Levy A, Cerutti P: Suppression of tumor promoter phorbolmyristate acetate-induced chromosome breakage by antioxidants and inhibitors of arachidonic acid metabolism. Mutat Res. 1983 Aug;110(2):327-35. doi: 10.1016/0027-5107(83)90149-5. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
  2. Flockhart Table of Drug Interactions [Link]
  3. Wang et al. (2004). Clin Pharmacol Ther. 75:191-197 [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
  2. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Triglyceride lipase activity
Specific Function
Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acy...
Gene Name
CES1
Uniprot ID
P23141
Uniprot Name
Liver carboxylesterase 1
Molecular Weight
62520.62 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Retinoic acid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 2 lacks trans...
Gene Name
UGT1A9
Uniprot ID
O60656
Uniprot Name
UDP-glucuronosyltransferase 1-9
Molecular Weight
59940.495 Da
References
  1. Mano Y, Usui T, Kamimura H: Contribution of UDP-glucuronosyltransferases 1A9 and 2B7 to the glucuronidation of indomethacin in the human liver. Eur J Clin Pharmacol. 2007 Mar;63(3):289-96. Epub 2007 Jan 24. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
Molecular Weight
59590.91 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
  2. Mano Y, Usui T, Kamimura H: In vitro inhibitory effects of non-steroidal antiinflammatory drugs on UDP-glucuronosyltransferase 1A1-catalysed estradiol 3beta-glucuronidation in human liver microsomes. Biopharm Drug Dispos. 2005 Jan;26(1):35-9. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Glucuronosyltransferase activity
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.Its unique specificity for 3,4-catechol estrogens and estriol su...
Gene Name
UGT2B7
Uniprot ID
P16662
Uniprot Name
UDP-glucuronosyltransferase 2B7
Molecular Weight
60694.12 Da
References
  1. Mano Y, Usui T, Kamimura H: Contribution of UDP-glucuronosyltransferases 1A9 and 2B7 to the glucuronidation of indomethacin in the human liver. Eur J Clin Pharmacol. 2007 Mar;63(3):289-96. Epub 2007 Jan 24. [Article]
  2. Mano Y, Usui T, Kamimura H: Inhibitory potential of nonsteroidal anti-inflammatory drugs on UDP-glucuronosyltransferase 2B7 in human liver microsomes. Eur J Clin Pharmacol. 2007 Feb;63(2):211-6. Epub 2007 Jan 3. [Article]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Bertucci C, Wainer IW: Improved chromatographic performance of a modified human albumin based stationary phase. Chirality. 1997;9(4):335-40. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Organic anion transmembrane transporter activity
Specific Function
May act as an inducible transporter in the biliary and intestinal excretion of organic anions. Acts as an alternative route for the export of bile acids and glucuronides from cholestatic hepatocyte...
Gene Name
ABCC3
Uniprot ID
O15438
Uniprot Name
Canalicular multispecific organic anion transporter 2
Molecular Weight
169341.14 Da
References
  1. Zelcer N, Saeki T, Reid G, Beijnen JH, Borst P: Characterization of drug transport by the human multidrug resistance protein 3 (ABCC3). J Biol Chem. 2001 Dec 7;276(49):46400-7. [Article]
  2. Gedeon C, Behravan J, Koren G, Piquette-Miller M: Transport of glyburide by placental ABC transporters: implications in fetal drug exposure. Placenta. 2006 Nov-Dec;27(11-12):1096-102. Epub 2006 Feb 3. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Atpase activity, coupled to transmembrane movement of substances
Specific Function
May be an organic anion pump relevant to cellular detoxification.
Gene Name
ABCC4
Uniprot ID
O15439
Uniprot Name
Multidrug resistance-associated protein 4
Molecular Weight
149525.33 Da
References
  1. Reid G, Wielinga P, Zelcer N, van der Heijden I, Kuil A, de Haas M, Wijnholds J, Borst P: The human multidrug resistance protein MRP4 functions as a prostaglandin efflux transporter and is inhibited by nonsteroidal antiinflammatory drugs. Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9244-9. Epub 2003 Jun 30. [Article]
  2. Bai J, Lai L, Yeo HC, Goh BC, Tan TM: Multidrug resistance protein 4 (MRP4/ABCC4) mediates efflux of bimane-glutathione. Int J Biochem Cell Biol. 2004 Feb;36(2):247-57. [Article]
  3. Ose A, Ito M, Kusuhara H, Yamatsugu K, Kanai M, Shibasaki M, Hosokawa M, Schuetz JD, Sugiyama Y: Limited brain distribution of [3R,4R,5S]-4-acetamido-5-amino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate phosphate (Ro 64-0802), a pharmacologically active form of oseltamivir, by active efflux across the blood-brain barrier mediated by organic anion transporter 3 (Oat3/Slc22a8) and multidrug resistance-associated protein 4 (Mrp4/Abcc4). Drug Metab Dispos. 2009 Feb;37(2):315-21. doi: 10.1124/dmd.108.024018. Epub 2008 Nov 24. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transporter activity
Specific Function
Isoform 1: May participate directly in the active transport of drugs into subcellular organelles or influence drug distribution indirectly. Transports glutathione conjugates as leukotriene-c4 (LTC4...
Gene Name
ABCC6
Uniprot ID
O95255
Uniprot Name
Multidrug resistance-associated protein 6
Molecular Weight
164904.81 Da
References
  1. Ilias A, Urban Z, Seidl TL, Le Saux O, Sinko E, Boyd CD, Sarkadi B, Varadi A: Loss of ATP-dependent transport activity in pseudoxanthoma elasticum-associated mutants of human ABCC6 (MRP6). J Biol Chem. 2002 May 10;277(19):16860-7. Epub 2002 Mar 5. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Wang EJ, Casciano CN, Clement RP, Johnson WW: Active transport of fluorescent P-glycoprotein substrates: evaluation as markers and interaction with inhibitors. Biochem Biophys Res Commun. 2001 Nov 30;289(2):580-5. [Article]
  2. Faassen F, Vogel G, Spanings H, Vromans H: Caco-2 permeability, P-glycoprotein transport ratios and brain penetration of heterocyclic drugs. Int J Pharm. 2003 Sep 16;263(1-2):113-22. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transporter activity
Specific Function
Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotre...
Gene Name
ABCC1
Uniprot ID
P33527
Uniprot Name
Multidrug resistance-associated protein 1
Molecular Weight
171589.5 Da
References
  1. Evers R, de Haas M, Sparidans R, Beijnen J, Wielinga PR, Lankelma J, Borst P: Vinblastine and sulfinpyrazone export by the multidrug resistance protein MRP2 is associated with glutathione export. Br J Cancer. 2000 Aug;83(3):375-83. [Article]
  2. Hong J, Lambert JD, Lee SH, Sinko PJ, Yang CS: Involvement of multidrug resistance-associated proteins in regulating cellular levels of (-)-epigallocatechin-3-gallate and its methyl metabolites. Biochem Biophys Res Commun. 2003 Oct 10;310(1):222-7. [Article]
  3. Ilias A, Urban Z, Seidl TL, Le Saux O, Sinko E, Boyd CD, Sarkadi B, Varadi A: Loss of ATP-dependent transport activity in pseudoxanthoma elasticum-associated mutants of human ABCC6 (MRP6). J Biol Chem. 2002 May 10;277(19):16860-7. Epub 2002 Mar 5. [Article]
  4. Reid G, Wielinga P, Zelcer N, van der Heijden I, Kuil A, de Haas M, Wijnholds J, Borst P: The human multidrug resistance protein MRP4 functions as a prostaglandin efflux transporter and is inhibited by nonsteroidal antiinflammatory drugs. Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9244-9. Epub 2003 Jun 30. [Article]
  5. Gedeon C, Behravan J, Koren G, Piquette-Miller M: Transport of glyburide by placental ABC transporters: implications in fetal drug exposure. Placenta. 2006 Nov-Dec;27(11-12):1096-102. Epub 2006 Feb 3. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity). Selectively inhibit...
Gene Name
SLCO1A2
Uniprot ID
P46721
Uniprot Name
Solute carrier organic anion transporter family member 1A2
Molecular Weight
74144.105 Da
References
  1. Shitara Y, Sugiyama D, Kusuhara H, Kato Y, Abe T, Meier PJ, Itoh T, Sugiyama Y: Comparative inhibitory effects of different compounds on rat oatpl (slc21a1)- and Oatp2 (Slc21a5)-mediated transport. Pharm Res. 2002 Feb;19(2):147-53. [Article]
  2. Kouzuki H, Suzuki H, Sugiyama Y: Pharmacokinetic study of the hepatobiliary transport of indomethacin. Pharm Res. 2000 Apr;17(4):432-8. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Curator comments
Substrate profile was demonstrated in vitro using human OAT1 expressed on S2 cells.
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
Molecular Weight
61815.78 Da
References
  1. Mulato AS, Ho ES, Cihlar T: Nonsteroidal anti-inflammatory drugs efficiently reduce the transport and cytotoxicity of adefovir mediated by the human renal organic anion transporter 1. J Pharmacol Exp Ther. 2000 Oct;295(1):10-5. [Article]
  2. Jung KY, Takeda M, Kim DK, Tojo A, Narikawa S, Yoo BS, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of ochratoxin A transport by human organic anion transporters. Life Sci. 2001 Sep 21;69(18):2123-35. [Article]
  3. Takeda M, Khamdang S, Narikawa S, Kimura H, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of methotrexate transport and its drug interactions with human organic anion transporters. J Pharmacol Exp Ther. 2002 Aug;302(2):666-71. [Article]
  4. Hosoyamada M, Sekine T, Kanai Y, Endou H: Molecular cloning and functional expression of a multispecific organic anion transporter from human kidney. Am J Physiol. 1999 Jan;276(1 Pt 2):F122-8. [Article]
  5. Lu R, Chan BS, Schuster VL: Cloning of the human kidney PAH transporter: narrow substrate specificity and regulation by protein kinase C. Am J Physiol. 1999 Feb;276(2 Pt 2):F295-303. [Article]
  6. Sandhu P, Lee W, Xu X, Leake BF, Yamazaki M, Stone JA, Lin JH, Pearson PG, Kim RB: Hepatic uptake of the novel antifungal agent caspofungin. Drug Metab Dispos. 2005 May;33(5):676-82. Epub 2005 Feb 16. [Article]
  7. Kuze K, Graves P, Leahy A, Wilson P, Stuhlmann H, You G: Heterologous expression and functional characterization of a mouse renal organic anion transporter in mammalian cells. J Biol Chem. 1999 Jan 15;274(3):1519-24. [Article]
  8. Uwai Y, Saito H, Inui K: Interaction between methotrexate and nonsteroidal anti-inflammatory drugs in organic anion transporter. Eur J Pharmacol. 2000 Dec 1;409(1):31-6. [Article]
  9. Apiwattanakul N, Sekine T, Chairoungdua A, Kanai Y, Nakajima N, Sophasan S, Endou H: Transport properties of nonsteroidal anti-inflammatory drugs by organic anion transporter 1 expressed in Xenopus laevis oocytes. Mol Pharmacol. 1999 May;55(5):847-54. [Article]
  10. VanWert AL, Gionfriddo MR, Sweet DH: Organic anion transporters: discovery, pharmacology, regulation and roles in pathophysiology. Biopharm Drug Dispos. 2010 Jan;31(1):1-71. doi: 10.1002/bdd.693. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Solute carrier family 22 member 8
Molecular Weight
59855.585 Da
References
  1. Cha SH, Sekine T, Fukushima JI, Kanai Y, Kobayashi Y, Goya T, Endou H: Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney. Mol Pharmacol. 2001 May;59(5):1277-86. [Article]
  2. Jung KY, Takeda M, Kim DK, Tojo A, Narikawa S, Yoo BS, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of ochratoxin A transport by human organic anion transporters. Life Sci. 2001 Sep 21;69(18):2123-35. [Article]
  3. Takeda M, Khamdang S, Narikawa S, Kimura H, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of methotrexate transport and its drug interactions with human organic anion transporters. J Pharmacol Exp Ther. 2002 Aug;302(2):666-71. [Article]
  4. Ohtsuki S, Kikkawa T, Mori S, Hori S, Takanaga H, Otagiri M, Terasaki T: Mouse reduced in osteosclerosis transporter functions as an organic anion transporter 3 and is localized at abluminal membrane of blood-brain barrier. J Pharmacol Exp Ther. 2004 Jun;309(3):1273-81. Epub 2004 Feb 4. [Article]
  5. Mori S, Takanaga H, Ohtsuki S, Deguchi T, Kang YS, Hosoya K, Terasaki T: Rat organic anion transporter 3 (rOAT3) is responsible for brain-to-blood efflux of homovanillic acid at the abluminal membrane of brain capillary endothelial cells. J Cereb Blood Flow Metab. 2003 Apr;23(4):432-40. [Article]
  6. Kusuhara H, Sekine T, Utsunomiya-Tate N, Tsuda M, Kojima R, Cha SH, Sugiyama Y, Kanai Y, Endou H: Molecular cloning and characterization of a new multispecific organic anion transporter from rat brain. J Biol Chem. 1999 May 7;274(19):13675-80. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Organic anion transmembrane transporter activity
Specific Function
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name
ABCC2
Uniprot ID
Q92887
Uniprot Name
Canalicular multispecific organic anion transporter 1
Molecular Weight
174205.64 Da
References
  1. Gedeon C, Behravan J, Koren G, Piquette-Miller M: Transport of glyburide by placental ABC transporters: implications in fetal drug exposure. Placenta. 2006 Nov-Dec;27(11-12):1096-102. Epub 2006 Feb 3. [Article]
  2. Dahan A, Amidon GL: Small intestinal efflux mediated by MRP2 and BCRP shifts sulfasalazine intestinal permeability from high to low, enabling its colonic targeting. Am J Physiol Gastrointest Liver Physiol. 2009 Aug;297(2):G371-7. doi: 10.1152/ajpgi.00102.2009. Epub 2009 Jun 18. [Article]
  3. Dahan A, Sabit H, Amidon GL: The H2 receptor antagonist nizatidine is a P-glycoprotein substrate: characterization of its intestinal epithelial cell efflux transport. AAPS J. 2009 Jun;11(2):205-13. doi: 10.1208/s12248-009-9092-5. Epub 2009 Mar 25. [Article]
  4. Kouzuki H, Suzuki H, Sugiyama Y: Pharmacokinetic study of the hepatobiliary transport of indomethacin. Pharm Res. 2000 Apr;17(4):432-8. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Purine nucleotide transmembrane transporter activity
Specific Function
Participates in physiological processes involving bile acids, conjugated steroids and cyclic nucleotides. Enhances the cellular extrusion of cAMP and cGMP. Stimulates the ATP-dependent uptake of a ...
Gene Name
ABCC11
Uniprot ID
Q96J66
Uniprot Name
ATP-binding cassette sub-family C member 11
Molecular Weight
154299.625 Da
References
  1. Chen ZS, Guo Y, Belinsky MG, Kotova E, Kruh GD: Transport of bile acids, sulfated steroids, estradiol 17-beta-D-glucuronide, and leukotriene C4 by human multidrug resistance protein 8 (ABCC11). Mol Pharmacol. 2005 Feb;67(2):545-57. Epub 2004 Nov 10. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates saturable uptake of estrone sulfate, dehydroepiandrosterone sulfate and related compounds.
Gene Name
SLC22A11
Uniprot ID
Q9NSA0
Uniprot Name
Solute carrier family 22 member 11
Molecular Weight
59970.945 Da
References
  1. Babu E, Takeda M, Narikawa S, Kobayashi Y, Enomoto A, Tojo A, Cha SH, Sekine T, Sakthisekaran D, Endou H: Role of human organic anion transporter 4 in the transport of ochratoxin A. Biochim Biophys Acta. 2002 Jun 12;1590(1-3):64-75. [Article]
  2. Takeda M, Khamdang S, Narikawa S, Kimura H, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of methotrexate transport and its drug interactions with human organic anion transporters. J Pharmacol Exp Ther. 2002 Aug;302(2):666-71. [Article]
  3. Cha SH, Sekine T, Kusuhara H, Yu E, Kim JY, Kim DK, Sugiyama Y, Kanai Y, Endou H: Molecular cloning and characterization of multispecific organic anion transporter 4 expressed in the placenta. J Biol Chem. 2000 Feb 11;275(6):4507-12. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Virus receptor activity
Specific Function
The hepatic sodium/bile acid uptake system exhibits broad substrate specificity and transports various non-bile acid organic compounds as well. It is strictly dependent on the extracellular presenc...
Gene Name
SLC10A1
Uniprot ID
Q14973
Uniprot Name
Sodium/bile acid cotransporter
Molecular Weight
38118.64 Da
References
  1. Kouzuki H, Suzuki H, Sugiyama Y: Pharmacokinetic study of the hepatobiliary transport of indomethacin. Pharm Res. 2000 Apr;17(4):432-8. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates sodium-independent multispecific organic anion transport. Transport of prostaglandin E2, prostaglandin F2, tetracycline, bumetanide, estrone sulfate, glutarate, dehydroepiandrosterone sulf...
Gene Name
SLC22A7
Uniprot ID
Q9Y694
Uniprot Name
Solute carrier family 22 member 7
Molecular Weight
60025.025 Da
References
  1. Morita N, Kusuhara H, Sekine T, Endou H, Sugiyama Y: Functional characterization of rat organic anion transporter 2 in LLC-PK1 cells. J Pharmacol Exp Ther. 2001 Sep;298(3):1179-84. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. Karlgren M, Ahlin G, Bergstrom CA, Svensson R, Palm J, Artursson P: In vitro and in silico strategies to identify OATP1B1 inhibitors and predict clinical drug-drug interactions. Pharm Res. 2012 Feb;29(2):411-26. doi: 10.1007/s11095-011-0564-9. Epub 2011 Aug 23. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Transporter activity
Specific Function
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name
ABCB11
Uniprot ID
O95342
Uniprot Name
Bile salt export pump
Molecular Weight
146405.83 Da
References
  1. Pedersen JM, Matsson P, Bergstrom CA, Hoogstraate J, Noren A, LeCluyse EL, Artursson P: Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43. doi: 10.1093/toxsci/kft197. Epub 2013 Sep 6. [Article]

Drug created at June 13, 2005 13:24 / Updated at March 18, 2024 16:48