Identification

Name
Etodolac
Accession Number
DB00749  (APRD00067)
Type
Small Molecule
Groups
Approved, Investigational, Vet approved
Description

Etodolac is a non-steroidal anti-inflammatory drug (NSAID) with anti-inflammatory, analgesic and antipyretic properties. Its therapeutic effects are due to its ability to inhibit prostaglandin synthesis. It is indicated for relief of signs and symptoms of rheumatoid arthritis and osteoarthritis.

Structure
Thumb
Synonyms
  • (+-)-1,8-Diethyl-1,3,4,9-tetrahydropyrano(3,4-b)indole-1-acetic acid
  • (1,8-Diethyl-1,3,4,9-tetrahydro-pyrano[3,4-b]indol-1-yl)-acetic acid
  • 1,3,4,9-Tetrahydro-1,8-diethylpyrano(3,4-b)indole-1-acetic acid
  • 1,8-Diethyl-1,3,4,9-tetrahydropyrano(3,4-b)indole-1-acetic acid
  • 1,8-Diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indol-1-ylacetic acid
  • Étodolac
  • Etodolac
  • Etodolaco
  • Etodolacum
  • Etodolic acid
  • Etodolsäure
External IDs
AY 24236
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
EtodolacCapsule200 mgOralAa Pharma Inc1997-08-21Not applicableCanada
EtodolacCapsule300 mgOralAa Pharma Inc1997-08-21Not applicableCanada
LodineTablet400 mg/1OralPhysicians Total Care, Inc.1993-10-152011-05-31Us
LodineCapsule300 mg/1OralPhysicians Total Care, Inc.1994-01-032002-06-30Us
LodineTablet500 mg/1OralPhysicians Total Care, Inc.1996-10-012011-05-31Us
Ultradol - Cap 200mgCapsule200 mgOralProcter And Gamble1995-12-312002-07-23Canada
Ultradol - Cap 300mgCapsule300 mgOralProcter And Gamble1995-12-312008-09-09Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
EtodolacTablet, film coated400 mg/1OralPD-Rx Pharmaceuticals, Inc.1998-05-202018-08-23Us
EtodolacTablet, coated500 mg/1OralPreferreed Pharmaceuticals Inc.2015-04-20Not applicableUs
EtodolacTablet, film coated500 mg/1OralTaro Pharmaceuticals U.S.A., Inc.2000-04-25Not applicableUs51672 403620180907 15195 5vfjkd
EtodolacTablet, film coated400 mg/1OralLake Erie Medical &Surgical Supply Dba Quality Care Products Llc1998-03-11Not applicableUs
EtodolacTablet, film coated400 mg/1OralA-S Medication Solutions2003-05-01Not applicableUs54569 446820180907 15195 1qtc1qi
EtodolacTablet500 mg/1OralGenpharm Ulc2015-11-012015-11-24Us
EtodolacTablet, film coated400 mg/1OralA-S Medication Solutions1998-05-202017-01-31Us50090 058720180907 15195 1xvv6md
EtodolacCapsule300 mg/1OralPd Rx Pharmaceuticals, Inc.1998-04-30Not applicableUs
EtodolacTablet, coated400 mg/1OralAmerincan Health Packaging2016-01-292018-07-31Us
EtodolacCapsule300 mg/1OralRed Pharm Drug, Inc.2015-02-01Not applicableUs
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
NuDroxiPAK E-400Etodolac (400 mg/1) + Capsaicin (0.25 mg/1mL) + Menthol (60 mg/1mL) + Methyl salicylate (250 mg/1mL)KitOralNucare Pharmaceuticals,inc.2018-03-16Not applicableUs
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
LodineEtodolac (500 mg/1)Tablet, film coatedOralWyeth Pharmaceuticals Inc.2006-03-30Not applicableUs
LodineEtodolac (200 mg/1)CapsuleOralWyeth Pharmaceuticals Inc.2006-03-30Not applicableUs
LodineEtodolac (400 mg/1)Tablet, film coatedOralWyeth Pharmaceuticals Inc.2006-03-30Not applicableUs
LodineEtodolac (300 mg/1)CapsuleOralWyeth Pharmaceuticals Inc.2006-03-30Not applicableUs
International/Other Brands
Bodopine (Yuan Chou) / Dolarit (Drogsan) / Dolchis (Korea United Pharm) / Doloc (Unifarma) / Dualgan (ITF) / Eccoxolac (Meda) / Edolar Fort (Pfizer) / Edopain (Incepta) / Edopain ER (Incepta) / Elac (Royal) / Elderin (Lek) / Eric (U.C. Pharma) / Esodax (Münir Sahin) / ETL (Senton) / Etodin (Nobel) / Etodin Fort (Ulkar) / Etodol (Yuhan) / Etodon (Shinlon) / Etoflam (Standard Chem) / Etol Fort (Nobel) / Etolac (Alkaloid) / Etomax (Ipca) / Etomax-ER (Ipca) / Etonox (Charoen Bhaesaj) / Etopan (Winthrop Pharmaceuticals) / Etopin (U-Liang) / Lodine XL (Wyeth)
Categories
UNII
2M36281008
CAS number
41340-25-4
Weight
Average: 287.3535
Monoisotopic: 287.152143543
Chemical Formula
C17H21NO3
InChI Key
NNYBQONXHNTVIJ-UHFFFAOYSA-N
InChI
InChI=1S/C17H21NO3/c1-3-11-6-5-7-12-13-8-9-21-17(4-2,10-14(19)20)16(13)18-15(11)12/h5-7,18H,3-4,8-10H2,1-2H3,(H,19,20)
IUPAC Name
2-{1,8-diethyl-1H,3H,4H,9H-pyrano[3,4-b]indol-1-yl}acetic acid
SMILES
CCC1=C2NC3=C(CCOC3(CC)CC(O)=O)C2=CC=C1

Pharmacology

Indication

For acute and long-term management of signs and symptoms of osteoarthritis and rheumatoid arthritis, as well as for the management of pain.

Associated Conditions
Pharmacodynamics

Etodolac is an anti-inflammatory agent with analgesic and antipyretic properties. It is used to treat osteoarthritis, rheumatoid arthritis and control acute pain. The therapeutic effects of etodolac are achieved via inhibition of the synthesis of prostaglandins involved in fever, pain, swelling and inflammation. Etodolac is administered as a racemate. As with other NSAIDs, the S-form has been shown to be active while the R-form is inactive. Both enantiomers are stable and there is no evidence of R- to S- conversion in vivo.

Mechanism of action

Similar to other NSAIDs, the anti-inflammatory effects of etodolac result from inhibition of the enzyme cycooxygenase (COX). This decreases the synthesis of peripheral prostaglandins involved in mediating inflammation. Etodolac binds to the upper portion of the COX enzyme active site and prevents its substrate, arachidonic acid, from entering the active site. Etodolac was previously thought to be a non-selective COX inhibitor, but it is now known to be 5 – 50 times more selective for COX-2 than COX-1. Antipyresis may occur by central action on the hypothalamus, resulting in peripheral dilation, increased cutaneous blood flow, and subsequent heat loss.

TargetActionsOrganism
AProstaglandin G/H synthase 2
inhibitor
Human
UProstaglandin G/H synthase 1
inhibitor
Human
URetinoic acid receptor RXR-alpha
other
Human
Absorption

Based on mass balance studies, the systemic bioavailability of etodolac from either the tablet or capsule formulation is at least 80%.

Volume of distribution
  • 390 mL/kg
Protein binding

> 99% bound, primarily to albumin

Metabolism

Etodolac is extensively metabolized in the liver. Renal elimination of etodolac and its metabolites is the primary route of excretion (72%). Metabolites found in urine (with percents of the administered dose) are: unchanged etodolac (1%), etodolac glucuronide (13%), hydroxylated metabolites (6-, 7-, and 8-OH; 5%), hydroxylated metabolite glucuronides (20%), and unidentified metabolites (33%). Fecal excretion accounts for 16% of its elimination.

Route of elimination

It is not known whether etodolac is excreted in human milk; however, based on its physical-chemical properties, excretion into breast milk is expected. Etodolac is extensively metabolized in the liver. The hydroxylated-etodolac metabolites undergo further glucuronidation followed by renal excretion and partial elimination in the feces (16% of dose). Approximately 1% of a etodolac dose is excreted unchanged in the urine with 72% of the dose excreted into urine as parent drug plus metabolite.

Half life

Terminal t1/2, 7.3 ± 4.0 hours. Distribution t1/2, 0.71 ± 0.50 hours

Clearance
  • Oral cl=49.1 mL/h/kg [Normal healthy adults]
  • Oral cl=49.4 mL/h/kg [Healthy males (18-65 years)]
  • Oral cl=35.7 mL/h/kg [Healthy females (27-65 years)]
  • Oral cl=45.7 mL/h/kg [Eldery (>65 years)]
  • Oral cl=58.3 mL/h/kg [Renal impairement (46-73 years)]
  • Oral cl=42.0 mL/h/kg [Hepatic impairement (34-60 years)]
Toxicity

Selective COX-2 inhibitors have been associated with increased risk of serious cardiovascular events (e.g. myocardial infarction, stroke) in some patients. Current data is insufficient to assess the cardiovascular risk of etodolac. Etodolac may increase blood pressure and/or cause fluid retention and edema. Risk of GI toxicity including bleeding, ulceration and perforation. Risk of direct renal injury, including renal papillary necrosis. Anaphylactoid and serious skin reactions (e.g. exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) have been reported. Common adverse events include abdominal pain, constipation, diarrhea, dyspepsia, flatulence, GI bleeding, GI perforation, nausea, peptic ulcer, vomiting, renal function abnormalities, anemia, dizziness, edema, liver function test abnormalities, headache, prolonged bleeding time, pruritus, rash, tinnitus. Symptoms of overdose include lethargy, drowsiness, nausea, vomiting, and epigastric pain.

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Etodolac Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(4R)-limoneneThe risk or severity of adverse effects can be increased when (4R)-limonene is combined with Etodolac.
16-BromoepiandrosteroneThe risk or severity of adverse effects can be increased when Etodolac is combined with 16-Bromoepiandrosterone.
19-norandrostenedioneThe risk or severity of adverse effects can be increased when Etodolac is combined with 19-norandrostenedione.
5-androstenedioneThe risk or severity of adverse effects can be increased when Etodolac is combined with 5-androstenedione.
AbciximabThe risk or severity of bleeding and hemorrhage can be increased when Etodolac is combined with Abciximab.
AbirateroneThe metabolism of Etodolac can be decreased when combined with Abiraterone.
AcebutololEtodolac may decrease the antihypertensive activities of Acebutolol.
AceclofenacThe risk or severity of adverse effects can be increased when Etodolac is combined with Aceclofenac.
AcemetacinThe risk or severity of adverse effects can be increased when Etodolac is combined with Acemetacin.
AcenocoumarolEtodolac may increase the anticoagulant activities of Acenocoumarol.
Food Interactions
  • Avoid alcohol.
  • Food increases the peak plasma concentration of extended-release tablets with no effect on extent of absorption.
  • Food increases the time to peak concentration of regular release oral formulations by 1.4 to 3.8 hours with no effect on extent of absorption.
  • Take with food to reduce gastric irritation.

References

Synthesis Reference

Christopher A. Demerson, Leslie G. Humber, "Process for preparing 1,8-diethyl-1,3,4,9-tetrahydropyrano(3,4-b)-indole-1-acetic acid, etodolac." U.S. Patent US4585877, issued May, 1977.

US4585877
General References
Not Available
External Links
Human Metabolome Database
HMDB0014887
KEGG Drug
D00315
KEGG Compound
C06991
PubChem Compound
3308
PubChem Substance
46505184
ChemSpider
3192
BindingDB
50016799
ChEBI
4909
ChEMBL
CHEMBL622
Therapeutic Targets Database
DAP000778
PharmGKB
PA449550
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Etodolac
ATC Codes
M01AB08 — Etodolac
AHFS Codes
  • 28:08.04.92 — Other Nonsteroidal Antiimflammatory Agents
FDA label
Download (290 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentFasting3
1CompletedTreatmentHealthy Volunteers1
2TerminatedTreatmentProstatic Neoplasms1
3CompletedTreatmentAnkle Sprains1
3CompletedTreatmentPost Operative Pain1
3Not Yet RecruitingTreatmentPain, Acute1
3Unknown StatusPreventionNeoplasms, Colorectal1
4CompletedTreatmentMedicaments Substances in Therapeutic Use1
Not AvailableCompletedTreatmentKnee Osteoarthritis (Knee OA)1
Not AvailableUnknown StatusPreventionPrimary Operable Breast Cancer1

Pharmacoeconomics

Manufacturers
  • Aaipharma llc
  • Apotex inc
  • Endo pharmaceuticals inc
  • Genpharm inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Mylan pharmaceuticals inc
  • Sandoz inc
  • Taro pharmaceutical industries ltd
  • Teva pharmaceuticals usa inc
  • Watson laboratories inc
  • Wyeth pharmaceuticals inc
  • Point holdings inc
  • Watson laboratories inc florida
  • Actavis elizabeth llc
  • Apotex inc etobicoke site
  • Mylan laboratories inc
  • Ranbaxy laboratories ltd
Packagers
  • Actavis Group
  • Apotex Inc.
  • Apotheca Inc.
  • A-S Medication Solutions LLC
  • Atlantic Biologicals Corporation
  • Bristol-Myers Squibb Co.
  • Bryant Ranch Prepack
  • Corepharma LLC
  • DHHS Program Support Center Supply Service Center
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Eon Labs
  • H.J. Harkins Co. Inc.
  • Innoviant Pharmacy Inc.
  • Ivax Pharmaceuticals
  • Kaiser Foundation Hospital
  • Keltman Pharmaceuticals Inc.
  • Lake Erie Medical and Surgical Supply
  • Letco Medical Inc.
  • Major Pharmaceuticals
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Novopharm Ltd.
  • Nucare Pharmaceuticals Inc.
  • Ohm Laboratories Inc.
  • Palmetto Pharmaceuticals Inc.
  • Par Pharmaceuticals
  • Patheon Inc.
  • PD-Rx Pharmaceuticals Inc.
  • Physicians Total Care Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepak Systems Inc.
  • Prescript Pharmaceuticals
  • Ranbaxy Laboratories
  • Rebel Distributors Corp.
  • Redpharm Drug
  • Remedy Repack
  • Resource Optimization and Innovation LLC
  • Southwood Pharmaceuticals
  • St Mary's Medical Park Pharmacy
  • Stat Rx Usa
  • Taro Pharmaceuticals USA
  • Teva Pharmaceutical Industries Ltd.
  • Torpharm Inc.
Dosage forms
FormRouteStrength
CapsuleOral200 mg
CapsuleOral300 mg
Capsule, gelatin coatedOral300 mg/1
TabletOral400 mg/1
TabletOral500 mg/1
Tablet, coatedOral400 mg/1
Tablet, coatedOral500 mg/1
Tablet, extended releaseOral400 mg/1
Tablet, extended releaseOral500 mg/1
Tablet, extended releaseOral600 mg/1
Tablet, film coated, extended releaseOral400 mg/1
Tablet, film coated, extended releaseOral500 mg/1
Tablet, film coated, extended releaseOral600 mg/1
CapsuleOral200 mg/1
CapsuleOral300 mg/1
Tablet, film coatedOral400 mg/1
Tablet, film coatedOral500 mg/1
KitOral
Prices
Unit descriptionCostUnit
Etodolac CR 600 mg 24 Hour tablet2.76USD tablet
Lodine 400 mg tablet2.65USD tablet
Lodine 500 mg tablet1.8USD tablet
Etodolac CR 500 mg 24 Hour tablet1.6USD tablet
Etodolac 500 mg tablet1.52USD tablet
Etodolac 400 mg tablet1.5USD tablet
Etodolac CR 400 mg 24 Hour tablet1.46USD tablet
Etodolac 300 mg capsule1.31USD capsule
Apo-Etodolac 200 mg Capsule0.8USD capsule
Apo-Etodolac 300 mg Capsule0.8USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)146.5 °CPhysProp
water solubility16 mg/LNot Available
logP2.5Not Available
pKa4.65Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0392 mg/mLALOGPS
logP3.39ALOGPS
logP3.44ChemAxon
logS-3.9ALOGPS
pKa (Strongest Acidic)4.73ChemAxon
pKa (Strongest Basic)-4.2ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area62.32 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity81.16 m3·mol-1ChemAxon
Polarizability31.94 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9971
Blood Brain Barrier+0.9065
Caco-2 permeable+0.5726
P-glycoprotein substrateSubstrate0.7462
P-glycoprotein inhibitor INon-inhibitor0.9242
P-glycoprotein inhibitor IINon-inhibitor0.8988
Renal organic cation transporterNon-inhibitor0.8178
CYP450 2C9 substrateNon-substrate0.8545
CYP450 2D6 substrateNon-substrate0.7567
CYP450 3A4 substrateNon-substrate0.5
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6904
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.9453
BiodegradationNot ready biodegradable0.9835
Rat acute toxicity3.4536 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9808
hERG inhibition (predictor II)Non-inhibitor0.7763
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-000l-0090000000-cb5392bab35da402835e
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0006-0090000000-66382e8a032519cc0610
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-03di-0090000000-1ab9e4ff7d60e90eca2c
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-03di-0290000000-308131d28773ab2c9701
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-03dj-0890000000-ba74bd4789a5df9d1095
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-01pk-0920000000-3003d9d94ce99518b55e
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-000i-0090000000-1644ab62d0cb24cc769e
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-000f-0090000000-0d0a55600dd433d684b1
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-01ox-0090000000-17b2c48a871d73f3071a
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-03di-0290000000-fe771b5ef7a99c3f79dd
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-03dj-0980000000-50aec638935d673b713e
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00di-0910000000-ca92c4a042f65a5a6c9e
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00di-0920000000-22f891e69de842afb76f
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00di-0910000000-3903a65f3f64f26aa9b7
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-006x-0900000000-5bb09419198c9ca084c0
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0006-0900000000-61c0ea8a828fd0570b07
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0006-0900000000-4bec68aee4ff03d6d386
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-00dr-0890000000-e286df97fed2602fd759
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-00di-0920000000-0323497d51f9000f512d
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-00di-0910000000-4c9034687504f43ca35d
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-006x-1900000000-c7af982a125d43d0a322
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0006-1900000000-b6f0e91141ccbee49a24
LC-MS/MS Spectrum - LC-ESI-IT , positiveLC-MS/MSsplash10-00di-0930000000-16f06e354549b4eacb4c
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-00dr-0970000000-8693e29717fb7601dfab
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-00di-0940000000-d9875ccdb5dd4639af09
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-00dl-0910000000-c7918fc03d252733ba5b
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0006-0900000000-a45c507a9469f25641f1
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0006-0900000000-c71c8b6e48beac782768
MS/MS Spectrum - , positiveLC-MS/MSsplash10-006x-2910000000-096819f066d468e77974

Taxonomy

Description
This compound belongs to the class of organic compounds known as indolyl carboxylic acids and derivatives. These are compounds containing a carboxylic acid chain (of at least 2 carbon atoms) linked to an indole ring.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Indoles and derivatives
Sub Class
Indolyl carboxylic acids and derivatives
Direct Parent
Indolyl carboxylic acids and derivatives
Alternative Parents
3-alkylindoles / Benzenoids / Pyrroles / Heteroaromatic compounds / Oxacyclic compounds / Monocarboxylic acids and derivatives / Dialkyl ethers / Carboxylic acids / Azacyclic compounds / Organopnictogen compounds
show 4 more
Substituents
Indolyl carboxylic acid derivative / 3-alkylindole / Indole / Benzenoid / Pyrrole / Heteroaromatic compound / Oxacycle / Azacycle / Monocarboxylic acid or derivatives / Ether
show 12 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
monocarboxylic acid, organic heterotricyclic compound (CHEBI:4909)

Targets

Kind
Protein
Organism
Human
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. 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. Chen WS, Liu JH, Wei SJ, Liu JM, Hong CY, Yang WK: Colon cancer cells with high invasive potential are susceptible to induction of apoptosis by a selective COX-2 inhibitor. Cancer Sci. 2003 Mar;94(3):253-8. [PubMed:12824918]
  2. Chen WS, Wei SJ, Liu JM, Hsiao M, Kou-Lin J, Yang WK: Tumor invasiveness and liver metastasis of colon cancer cells correlated with cyclooxygenase-2 (COX-2) expression and inhibited by a COX-2-selective inhibitor, etodolac. Int J Cancer. 2001 Mar 15;91(6):894-9. [PubMed:11275997]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  4. Kusuhara H, Komatsu H, Sumichika H, Sugahara K: Reactive oxygen species are involved in the apoptosis induced by nonsteroidal anti-inflammatory drugs in cultured gastric cells. Eur J Pharmacol. 1999 Nov 3;383(3):331-7. [PubMed:10594327]
  5. Svendsen KB, Bech JN, Sorensen TB, Pedersen EB: A comparison of the effects of etodolac and ibuprofen on renal haemodynamics, tubular function, renin, vasopressin and urinary excretion of albumin and alpha-glutathione-S-transferase in healthy subjects: a placebo-controlled cross-over study. Eur J Clin Pharmacol. 2000 Aug;56(5):383-8. [PubMed:11009046]
  6. Wilson JE, Chandrasekharan NV, Westover KD, Eager KB, Simmons DL: Determination of expression of cyclooxygenase-1 and -2 isozymes in canine tissues and their differential sensitivity to nonsteroidal anti-inflammatory drugs. Am J Vet Res. 2004 Jun;65(6):810-8. [PubMed:15198222]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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...
Gene Name
PTGS1
Uniprot ID
P23219
Uniprot Name
Prostaglandin G/H synthase 1
Molecular Weight
68685.82 Da
References
  1. Campbell NB, Jones SL, Blikslager AT: The effects of cyclo-oxygenase inhibitors on bile-injured and normal equine colon. Equine Vet J. 2002 Jul;34(5):493-8. [PubMed:12358053]
  2. Glaser K, Sung ML, O'Neill K, Belfast M, Hartman D, Carlson R, Kreft A, Kubrak D, Hsiao CL, Weichman B: Etodolac selectively inhibits human prostaglandin G/H synthase 2 (PGHS-2) versus human PGHS-1. Eur J Pharmacol. 1995 Jul 25;281(1):107-11. [PubMed:8566109]
  3. Hirate K, Uchida A, Ogawa Y, Arai T, Yoda K: Zaltoprofen, a non-steroidal anti-inflammatory drug, inhibits bradykinin-induced pain responses without blocking bradykinin receptors. Neurosci Res. 2006 Apr;54(4):288-94. Epub 2006 Feb 13. [PubMed:16473424]
  4. Riendeau D, Percival MD, Boyce S, Brideau C, Charleson S, Cromlish W, Ethier D, Evans J, Falgueyret JP, Ford-Hutchinson AW, Gordon R, Greig G, Gresser M, Guay J, Kargman S, Leger S, Mancini JA, O'Neill G, Ouellet M, Rodger IW, Therien M, Wang Z, Webb JK, Wong E, Chan CC, et al.: Biochemical and pharmacological profile of a tetrasubstituted furanone as a highly selective COX-2 inhibitor. Br J Pharmacol. 1997 May;121(1):105-17. [PubMed:9146894]
  5. Wilson JE, Chandrasekharan NV, Westover KD, Eager KB, Simmons DL: Determination of expression of cyclooxygenase-1 and -2 isozymes in canine tissues and their differential sensitivity to nonsteroidal anti-inflammatory drugs. Am J Vet Res. 2004 Jun;65(6):810-8. [PubMed:15198222]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Other
General Function
Zinc ion binding
Specific Function
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expressi...
Gene Name
RXRA
Uniprot ID
P19793
Uniprot Name
Retinoic acid receptor RXR-alpha
Molecular Weight
50810.835 Da
References
  1. Kolluri SK, Corr M, James SY, Bernasconi M, Lu D, Liu W, Cottam HB, Leoni LM, Carson DA, Zhang XK: The R-enantiomer of the nonsteroidal antiinflammatory drug etodolac binds retinoid X receptor and induces tumor-selective apoptosis. Proc Natl Acad Sci U S A. 2005 Feb 15;102(7):2525-30. Epub 2005 Feb 7. [PubMed:15699354]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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. [PubMed:19515014]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
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. 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. [PubMed:19515014]
Kind
Protein
Organism
Human
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. Isoform 2 lacks transferase activity but acts as a negative reg...
Gene Name
UGT1A3
Uniprot ID
P35503
Uniprot Name
UDP-glucuronosyltransferase 1-3
Molecular Weight
60337.835 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. [PubMed:19515014]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Protein kinase c binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Isoform 2 lacks transferase activity but acts as a negative reg...
Gene Name
UGT1A10
Uniprot ID
Q9HAW8
Uniprot Name
UDP-glucuronosyltransferase 1-10
Molecular Weight
59809.075 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. [PubMed:19515014]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
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. 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. [PubMed:19515014]

Carriers

Kind
Protein
Organism
Human
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. Mignot I, Presle N, Lapicque F, Monot C, Dropsy R, Netter P: Albumin binding sites for etodolac enantiomers. Chirality. 1996;8(3):271-80. [PubMed:8777148]
  2. Muller N, Lapicque F, Monot C, Payan E, Dropsy R, Netter P: Stereoselective binding of etodolac to human serum albumin. Chirality. 1992;4(4):240-6. [PubMed:1389961]
  3. Smith PC, Song WQ, Rodriguez RJ: Covalent binding of etodolac acyl glucuronide to albumin in vitro. Drug Metab Dispos. 1992 Nov-Dec;20(6):962-5. [PubMed:1362954]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
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. [PubMed:10991954]

Drug created on June 13, 2005 07:24 / Updated on September 23, 2018 19:37