Rofecoxib

Identification

Summary

Rofecoxib is a COX-2 inhibitor NSAID used to treat osteoarthritis, rheumatoid arthritis, acute pain, primary dysmenorrhea, and migraine attacks.

Generic Name
Rofecoxib
DrugBank Accession Number
DB00533
Background

Rofecoxib is used for the treatment of osteoarthritis, rheumatoid arthritis, acute pain in adults, and primary dysmenorrhea, as well as acute treatment of migraine attacks with or without auras. Rofecoxib is a solid. This compound belongs to the stilbenes. These are organic compounds containing a 1,2-diphenylethylene moiety. Stilbenes (C6-C2-C6 ) are derived from the common phenylpropene (C6-C3) skeleton building block. The introduction of one or more hydroxyl groups to a phenyl ring lead to stilbenoids. Rofecoxib has a half-life of 17 hours and its mean oral bioavailability at therapeutically recommended doses of 125, 25, and 50 mg is approximately 93%. The proteins that rofecoxib target include elastin and prostaglandin G/H synthase 2. Cytochrome P450 1A2, Cytochrome P450 3A4, Cytochrome P450 2C9, Cytochrome P450 2C8, and Prostaglandin G/H synthase 1 are known to metabolize rofecoxib. On September 30, 2004, Merck voluntarily withdrew rofecoxib from the market because of concerns about increased risk of heart attack and stroke associated with long-term, high-dosage use.

Type
Small Molecule
Groups
Approved, Investigational, Withdrawn
Structure
Weight
Average: 314.356
Monoisotopic: 314.061279626
Chemical Formula
C17H14O4S
Synonyms
  • 3-phenyl-4-[4-(methylsulfonyl)phenyl]-2(5H)-furanone
  • 4-[4-(methylsulfonyl)phenyl]-3-phenyl-2(5H)-furanone
  • Rofecoxib
  • Rofécoxib
  • Rofecoxibum
External IDs
  • MK 966
  • MK 996
  • MK-0966
  • MK0966

Pharmacology

Indication

For the treatment of osteoarthritis, rheumatoid arthritis, acute pain in adults, and primary dysmenorrhea, as well as acute treatment of migraine attacks with or without auras.

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Pharmacodynamics

Rofecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is classified as a nonsteroidal anti-inflammatory drug (NSAID). Unlike celecoxib, rofecoxib lacks a sulfonamide chain and does not require CYP450 enzymes for metabolism. Like other NSAIDs, rofecoxib exhibits anti-inflammatory, analgesic, and antipyretic activity. NSAIDs appear to inhibit prostaglandin synthesis via the inhibition of cyclooxygenase (COX), which are responsible for catalyzing the formation of prostaglandins in the arachidonic acid pathyway. There are at least two isoenzymes, COX-1 and COX-2, that have been identified. Although the exact mechanisms have not been clearly established, NSAIDs exert their anti-inflammatory, analgesic, and antipyretic primarily through the inhibition of COX-2. The inhibition of COX-1 is principally responsible for the negative effects on the GI mucosa. As rofecoxib is selective for COX-2, it may be potentially associated with a decreased risk of certain adverse events, but more data is needed to fully evaulate the drug.

Mechanism of action

The anti-inflammatory, analgesic, and antipyretic effects of NSAIDs appear to result from the inhibition of prostaglandin synthesis. Although the exact mechanism of action has not been determined, these effects appear to be mediated through the inhibition of the COX-2 isoenzyme at the sites of inflammation with subsequent reduction in the synthesis of certain prostaglandins from their arachidonic acid precursors. Rofecoxib selectively inhibits the cyclooxygenase-2 (COX-2) enzyme, which is important for the mediation of inflammation and pain. Unlike non-selective NSAIDs, rofecoxib does not inhibit platelet aggregation. It also has little to no affinity for COX-1.

TargetActionsOrganism
AProstaglandin G/H synthase 2
inhibitor
Humans
UElastin
other/unknown
Humans
Absorption

The mean oral bioavailability of rofecoxib at therapeutically recommended doses of 12.5, 25, and 50 mg is approximately 93%.

Volume of distribution

Not Available

Protein binding

87%

Metabolism

Hepatic. Metabolism of rofecoxib is primarily mediated through reduction by cytosolic enzymes. The principal metabolic products are the cis-dihydro and trans-dihydro derivatives of rofecoxib, which account for nearly 56% of recovered radioactivity in the urine. An additional 8.8% of the dose was recovered as the glucuronide of the hydroxy derivative, a product of oxidative metabolism. The biotransformation of rofecoxib and this metabolite is reversible in humans to a limited extent (< 5%). These metabolites are inactive as COX-1 or COX-2 inhibitors. Cytochrome P450 plays a minor role in metabolism of rofecoxib.

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Route of elimination

Not Available

Half-life

17 hours

Clearance

Not Available

Adverse Effects
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Toxicity

No overdoses of rofecoxib were reported during clinical trials. Administration of single doses of rofecoxib 1000 mg to 6 healthy volunteers and multiple doses of 250 mg/day for 14 days to 75 healthy volunteers did not result in serious toxicity.

Pathways
PathwayCategory
Rofecoxib 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
AbacavirRofecoxib may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbametapirThe serum concentration of Rofecoxib can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Rofecoxib can be increased when combined with Abatacept.
AbciximabThe risk or severity of bleeding and hemorrhage can be increased when Rofecoxib is combined with Abciximab.
AbemaciclibThe metabolism of Abemaciclib can be increased when combined with Rofecoxib.
Food Interactions
  • Take separate from antacids. Taking rofecoxib with antacids can reduce the AUC and Cmax of rofecoxib, therefore consider separating their administration for optimal efficacy.
  • Take with or without food. The AUC and Cmax of rofecoxib tablets are not impacted by administration with food, however, the Tmax may be delayed. The food effect on the absorption of rofecoxib suspension formulation has not been studied according to the official product labeling.

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International/Other Brands
Vioxx
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Vioxx Suspension 12.5mg/5mlSuspension12.5 mg / 5 mLOralMerck Frosst Canada & Cie, Merck Frosst Canada & Co.2000-05-082004-09-30Canada flag
Vioxx Tab 12.5mgTablet12.5 mg / tabOralMerck Frosst Canada & Cie, Merck Frosst Canada & Co.1999-11-082004-09-30Canada flag
Vioxx Tab 25mgTablet25 mg / tabOralMerck Frosst Canada & Cie, Merck Frosst Canada & Co.1999-11-082004-09-30Canada flag

Categories

ATC Codes
M01AH02 — Rofecoxib
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as stilbenes. These are organic compounds containing a 1,2-diphenylethylene moiety. Stilbenes (C6-C2-C6 ) are derived from the common phenylpropene (C6-C3) skeleton building block. The introduction of one or more hydroxyl groups to a phenyl ring lead to stilbenoids.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Stilbenes
Sub Class
Not Available
Direct Parent
Stilbenes
Alternative Parents
Benzenesulfonyl compounds / Butenolides / Sulfones / Enoate esters / Lactones / Oxacyclic compounds / Monocarboxylic acids and derivatives / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
2-furanone / Alpha,beta-unsaturated carboxylic ester / Aromatic heteromonocyclic compound / Benzenesulfonyl group / Benzenoid / Carbonyl group / Carboxylic acid derivative / Carboxylic acid ester / Dihydrofuran / Enoate ester
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
sulfone, butenolide (CHEBI:8887)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
0QTW8Z7MCR
CAS number
162011-90-7
InChI Key
RZJQGNCSTQAWON-UHFFFAOYSA-N
InChI
InChI=1S/C17H14O4S/c1-22(19,20)14-9-7-12(8-10-14)15-11-21-17(18)16(15)13-5-3-2-4-6-13/h2-10H,11H2,1H3
IUPAC Name
4-(4-methanesulfonylphenyl)-3-phenyl-2,5-dihydrofuran-2-one
SMILES
CS(=O)(=O)C1=CC=C(C=C1)C1=C(C(=O)OC1)C1=CC=CC=C1

References

General References
  1. Bombardier C, Laine L, Reicin A, Shapiro D, Burgos-Vargas R, Davis B, Day R, Ferraz MB, Hawkey CJ, Hochberg MC, Kvien TK, Schnitzer TJ: Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N Engl J Med. 2000 Nov 23;343(21):1520-8, 2 p following 1528. [Article]
  2. Bresalier RS, Sandler RS, Quan H, Bolognese JA, Oxenius B, Horgan K, Lines C, Riddell R, Morton D, Lanas A, Konstam MA, Baron JA: Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med. 2005 Mar 17;352(11):1092-102. Epub 2005 Feb 15. [Article]
  3. Curfman GD, Morrissey S, Drazen JM: Expression of concern reaffirmed. N Engl J Med. 2006 Mar 16;354(11):1193. Epub 2006 Feb 22. [Article]
  4. Fitzgerald GA: Coxibs and cardiovascular disease. N Engl J Med. 2004 Oct 21;351(17):1709-11. Epub 2004 Oct 6. [Article]
  5. Karha J, Topol EJ: The sad story of Vioxx, and what we should learn from it. Cleve Clin J Med. 2004 Dec;71(12):933-4, 936, 938-9. [Article]
  6. Baron JA, Sandler RS, Bresalier RS, Lanas A, Morton DG, Riddell R, Iverson ER, Demets DL: Cardiovascular events associated with rofecoxib: final analysis of the APPROVe trial. Lancet. 2008 Nov 15;372(9651):1756-64. doi: 10.1016/S0140-6736(08)61490-7. Epub 2008 Oct 14. [Article]
  7. Matheson AJ, Figgitt DP: Rofecoxib: a review of its use in the management of osteoarthritis, acute pain and rheumatoid arthritis. Drugs. 2001;61(6):833-65. [Article]
  8. Hillson JL, Furst DE: Rofecoxib. Expert Opin Pharmacother. 2000 Jul;1(5):1053-66. [Article]
KEGG Drug
D00568
KEGG Compound
C07590
PubChem Compound
5090
PubChem Substance
46504787
ChemSpider
4911
BindingDB
22369
RxNav
232158
ChEBI
8887
ChEMBL
CHEMBL122
ZINC
ZINC000000007455
Therapeutic Targets Database
DAP001338
PharmGKB
PA451268
PDBe Ligand
RCX
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Rofecoxib
PDB Entries
5kir
FDA label
Download (291 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentAnalgesia1
4CompletedTreatmentBarrett's Esophagus1
4CompletedTreatmentRheumatoid Arthritis1
4TerminatedTreatmentAcute Pain1
4TerminatedTreatmentAdenomatous Polyps1

Pharmacoeconomics

Manufacturers
  • Merck research laboratories div merck co inc
Packagers
  • AQ Pharmaceuticals Inc.
  • Cardinal Health
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Murfreesboro Pharmaceutical Nursing Supply
  • Nucare Pharmaceuticals Inc.
  • PCA LLC
  • PD-Rx Pharmaceuticals Inc.
  • Redpharm Drug
  • Southwood Pharmaceuticals
  • Va Cmop Dallas
Dosage Forms
FormRouteStrength
SuspensionOral0.5 mg
Capsule, liquid filledOral25 mg
Tablet, film coatedOral50 mg
Capsule, liquid filledOral50 mg
SuspensionOral0.25 g
SuspensionOral0.5 g
TabletOral50 mg
TabletOral12.5 mg
TabletOral25 mg
TabletOral250000 mg
SuspensionOral
TabletOral
SuspensionOral2.5 mg
SuspensionOral12.5 mg / 5 mL
TabletOral12.5 mg / tab
TabletOral25 mg / tab
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5474995No1995-12-122013-06-24US flag
US6063811Yes2000-05-162017-11-06US flag
US5691374Yes1997-11-252015-11-18US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityInsolubleNot Available
logP3.2Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0106 mg/mLALOGPS
logP2.32ALOGPS
logP2.56Chemaxon
logS-4.5ALOGPS
pKa (Strongest Acidic)13.12Chemaxon
pKa (Strongest Basic)-7Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count3Chemaxon
Hydrogen Donor Count0Chemaxon
Polar Surface Area60.44 Å2Chemaxon
Rotatable Bond Count3Chemaxon
Refractivity84.08 m3·mol-1Chemaxon
Polarizability31.73 Å3Chemaxon
Number of Rings3Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9938
Blood Brain Barrier+0.6296
Caco-2 permeable-0.5696
P-glycoprotein substrateNon-substrate0.7186
P-glycoprotein inhibitor INon-inhibitor0.5401
P-glycoprotein inhibitor IINon-inhibitor0.922
Renal organic cation transporterNon-inhibitor0.7846
CYP450 2C9 substrateNon-substrate0.5807
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.5941
CYP450 1A2 substrateInhibitor0.5426
CYP450 2C9 inhibitorInhibitor0.6668
CYP450 2D6 inhibitorNon-inhibitor0.889
CYP450 2C19 inhibitorInhibitor0.6214
CYP450 3A4 inhibitorNon-inhibitor0.8508
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7596
Ames testNon AMES toxic0.6152
CarcinogenicityNon-carcinogens0.5754
BiodegradationNot ready biodegradable0.7716
Rat acute toxicity2.4527 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9848
hERG inhibition (predictor II)Non-inhibitor0.8932
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-MSsplash10-0601-0390000000-d4d8a8654a5376343cab
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-014i-0497000000-44320e93d610fb5074f5
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-014i-0496000000-06716b4dad8f8d33dee6
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-0006-2920000000-abe97627fbae89daa0db
MS/MS Spectrum - , positiveLC-MS/MSsplash10-014i-0497000000-44320e93d610fb5074f5
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0006-0300900000-8c21a5272c47622769e7
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0002-0390000000-b69da0c82250f1f81243
MS/MS Spectrum - , positiveLC-MS/MSsplash10-014i-0496000000-06716b4dad8f8d33dee6
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0006-2920000000-abe97627fbae89daa0db
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-014i-0019000000-97567bef704dfee01953
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-03di-0039000000-165ba47904169cae03c5
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-03di-0019000000-f1acac5f4906b861b365
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-014i-0389000000-b2a14816f21bc67370bc
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-004r-7090000000-abb62c21cc7576f194ba
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0ug3-1940000000-c4f7a0da04251c1cca13
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]-186.2284341
predicted
DarkChem Lite v0.1.0
[M-H]-185.5702341
predicted
DarkChem Lite v0.1.0
[M-H]-187.2760341
predicted
DarkChem Lite v0.1.0
[M-H]-168.17377
predicted
DeepCCS 1.0 (2019)
[M+H]+186.5210341
predicted
DarkChem Lite v0.1.0
[M+H]+185.7012341
predicted
DarkChem Lite v0.1.0
[M+H]+187.0254341
predicted
DarkChem Lite v0.1.0
[M+H]+170.53175
predicted
DeepCCS 1.0 (2019)
[M+Na]+186.2572341
predicted
DarkChem Lite v0.1.0
[M+Na]+185.3622341
predicted
DarkChem Lite v0.1.0
[M+Na]+187.1303341
predicted
DarkChem Lite v0.1.0
[M+Na]+177.63387
predicted
DeepCCS 1.0 (2019)

Targets

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Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
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Kind
Protein
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. 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. Ehrich EW, Schnitzer TJ, McIlwain H, Levy R, Wolfe F, Weisman M, Zeng Q, Morrison B, Bolognese J, Seidenberg B, Gertz BJ: Effect of specific COX-2 inhibition in osteoarthritis of the knee: a 6 week double blind, placebo controlled pilot study of rofecoxib. Rofecoxib Osteoarthritis Pilot Study Group. J Rheumatol. 1999 Nov;26(11):2438-47. [Article]
  2. Malmstrom K, Daniels S, Kotey P, Seidenberg BC, Desjardins PJ: Comparison of rofecoxib and celecoxib, two cyclooxygenase-2 inhibitors, in postoperative dental pain: a randomized, placebo- and active-comparator-controlled clinical trial. Clin Ther. 1999 Oct;21(10):1653-63. [Article]
  3. Langman MJ, Jensen DM, Watson DJ, Harper SE, Zhao PL, Quan H, Bolognese JA, Simon TJ: Adverse upper gastrointestinal effects of rofecoxib compared with NSAIDs. JAMA. 1999 Nov 24;282(20):1929-33. [Article]
  4. Pascucci RA: COX-2-specific inhibition: implications for clinical practice. J Am Osteopath Assoc. 1999 Nov;99(11 Suppl):S18-22. [Article]
  5. Hawkey C, Laine L, Simon T, Beaulieu A, Maldonado-Cocco J, Acevedo E, Shahane A, Quan H, Bolognese J, Mortensen E: Comparison of the effect of rofecoxib (a cyclooxygenase 2 inhibitor), ibuprofen, and placebo on the gastroduodenal mucosa of patients with osteoarthritis: a randomized, double-blind, placebo-controlled trial. The Rofecoxib Osteoarthritis Endoscopy Multinational Study Group. Arthritis Rheum. 2000 Feb;43(2):370-7. [Article]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  7. Ashok V, Dash C, Rohan TE, Sprafka JM, Terry PD: Selective cyclooxygenase-2 (COX-2) inhibitors and breast cancer risk. Breast. 2011 Feb;20(1):66-70. doi: 10.1016/j.breast.2010.07.004. Epub 2010 Aug 17. [Article]
  8. Baron JA, Sandler RS, Bresalier RS, Lanas A, Morton DG, Riddell R, Iverson ER, Demets DL: Cardiovascular events associated with rofecoxib: final analysis of the APPROVe trial. Lancet. 2008 Nov 15;372(9651):1756-64. doi: 10.1016/S0140-6736(08)61490-7. Epub 2008 Oct 14. [Article]
  9. Chakraborti AK, Garg SK, Kumar R, Motiwala HF, Jadhavar PS: Progress in COX-2 inhibitors: a journey so far. Curr Med Chem. 2010;17(15):1563-93. [Article]
  10. Matheson AJ, Figgitt DP: Rofecoxib: a review of its use in the management of osteoarthritis, acute pain and rheumatoid arthritis. Drugs. 2001;61(6):833-65. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Other/unknown
General Function
Extracellular matrix structural constituent
Specific Function
Major structural protein of tissues such as aorta and nuchal ligament, which must expand rapidly and recover completely. Molecular determinant of the late arterial morphogenesis, stabilizing arteri...
Gene Name
ELN
Uniprot ID
P15502
Uniprot Name
Elastin
Molecular Weight
68468.375 Da
References
  1. Oitate M, Hirota T, Koyama K, Inoue S, Kawai K, Ikeda T: Covalent binding of radioactivity from [14C]rofecoxib, but not [14C]celecoxib or [14C]CS-706, to the arterial elastin of rats. Drug Metab Dispos. 2006 Aug;34(8):1417-22. Epub 2006 May 5. [Article]
  2. Oitate M, Hirota T, Takahashi M, Murai T, Miura S, Senoo A, Hosokawa T, Oonishi T, Ikeda T: Mechanism for covalent binding of rofecoxib to elastin of rat aorta. J Pharmacol Exp Ther. 2007 Mar;320(3):1195-203. Epub 2006 Dec 12. [Article]
  3. Oitate M, Hirota T, Murai T, Miura S, Ikeda T: Covalent binding of rofecoxib, but not other cyclooxygenase-2 inhibitors, to allysine aldehyde in elastin of human aorta. Drug Metab Dispos. 2007 Oct;35(10):1846-52. Epub 2007 Jul 9. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
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. 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
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
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Backman JT, Filppula AM, Niemi M, Neuvonen PJ: Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions. Pharmacol Rev. 2016 Jan;68(1):168-241. doi: 10.1124/pr.115.011411. [Article]
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. Rodrigues AD: Impact of CYP2C9 genotype on pharmacokinetics: are all cyclooxygenase inhibitors the same? Drug Metab Dispos. 2005 Nov;33(11):1567-75. Epub 2005 Aug 23. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inducer
General Function
Vitamin d3 25-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 performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 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. VIOXX® (rofecoxib tablets and oral suspension) - FDA Label [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
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
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Wang B, Zhou SF: Synthetic and natural compounds that interact with human cytochrome P450 1A2 and implications in drug development. Curr Med Chem. 2009;16(31):4066-218. [Article]
  2. 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]
  3. Backman JT, Karjalainen MJ, Neuvonen M, Laitila J, Neuvonen PJ: Rofecoxib is a potent inhibitor of cytochrome P450 1A2: studies with tizanidine and caffeine in healthy subjects. Br J Clin Pharmacol. 2006 Sep;62(3):345-57. doi: 10.1111/j.1365-2125.2006.02653.x. [Article]

Transporters

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]

Drug created at June 13, 2005 13:24 / Updated at March 03, 2024 02:27