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Identification
NameRosiglitazone
Accession NumberDB00412  (APRD00403)
TypeSmall Molecule
GroupsApproved, Investigational
Description

Rosiglitazone is an anti-diabetic drug in the thiazolidinedione class of drugs. It is marketed by the pharmaceutical company GlaxoSmithKline as a stand-alone drug (Avandia) and in combination with metformin (Avandamet) or with glimepiride (Avandaryl). Like other thiazolidinediones, the mechanism of action of rosiglitazone is by activation of the intracellular receptor class of the peroxisome proliferator-activated receptors (PPARs), specifically PPARγ. Rosiglitazone is a selective ligand of PPARγ, and has no PPARα-binding action. Apart from its effect on insulin resistance, it appears to have an anti-inflammatory effect: nuclear factor kappa-B (NFκB) levels fall and inhibitor (IκB) levels increase in patients on rosiglitazone. Recent research has suggested that rosiglitazone may also be of benefit to a subset of patients with Alzheimer’s disease not expressing the ApoE4 allele. This is the subject of a clinical trial currently underway.

Structure
Thumb
Synonyms
(±)-5-[p-[2-(methyl-2-pyridylamino)ethoxy]benzyl]-2,4-thiazolidinedione
(RS)-5-{4-[2-(Methyl-2-pyridylamino)ethoxy]benzyl}-2,4-thiazolidinedion
Rosiglitazon
Rosiglitazona
Rosiglitazone
Rosiglitazonum
External Identifiers
  • BRL 49653 C
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Avandiatablet, film coated4 mg/1oralCardinal Health1999-05-29Not applicableUs
Avandiatablet, film coated2 mg/1oralGlaxo Smith Kline Llc2011-05-25Not applicableUs
Avandiatablet, film coated2 mg/1oralPhysicians Total Care, Inc.2005-05-13Not applicableUs
Avandiatablet, film coated8 mg/1oralPhysicians Total Care, Inc.2001-05-09Not applicableUs
Avandiatablet, film coated4 mg/1oralPhysicians Total Care, Inc.2006-02-07Not applicableUs
Avandiatablet8 mgoralGlaxosmithkline Inc2000-03-21Not applicableCanada
Avandiatablet4 mgoralGlaxosmithkline Inc2000-03-21Not applicableCanada
Avandiatablet2 mgoralGlaxosmithkline Inc2000-03-21Not applicableCanada
Avandiatablet, film coated8 mg/1oralCardinal Health1999-05-28Not applicableUs
Avandiatablet, film coated8 mg/1oralGlaxo Smith Kline Llc2011-05-252016-04-03Us
Avandia 2mgtablet, film coated2 mg/1oralGlaxo Smith Kline Llc2011-05-25Not applicableUs
Avandia 4mgtablet, film coated4 mg/1oralGlaxo Smith Kline Llc2011-05-25Not applicableUs
Avandia 8mgtablet, film coated8 mg/1oralGlaxo Smith Kline Llc2011-05-25Not applicableUs
Dom-rosiglitazonetablet8 mgoralDominion PharmacalNot applicableNot applicableCanada
Dom-rosiglitazonetablet4 mgoralDominion PharmacalNot applicableNot applicableCanada
Dom-rosiglitazonetablet2 mgoralDominion PharmacalNot applicableNot applicableCanada
Mylan-rosiglitazonetablet8 mgoralMylan Pharmaceuticals UlcNot applicableNot applicableCanada
Mylan-rosiglitazonetablet4 mgoralMylan Pharmaceuticals UlcNot applicableNot applicableCanada
Mylan-rosiglitazonetablet2 mgoralMylan Pharmaceuticals UlcNot applicableNot applicableCanada
PHL-rosiglitazonetablet2 mgoralPharmel IncNot applicableNot applicableCanada
PHL-rosiglitazonetablet4 mgoralPharmel IncNot applicableNot applicableCanada
PHL-rosiglitazonetablet8 mgoralPharmel IncNot applicableNot applicableCanada
PMS-rosiglitazonetablet8 mgoralPharmascience IncNot applicableNot applicableCanada
PMS-rosiglitazonetablet4 mgoralPharmascience IncNot applicableNot applicableCanada
PMS-rosiglitazonetablet2 mgoralPharmascience IncNot applicableNot applicableCanada
Teva-rosiglitazonetablet2 mgoralTeva Canada LimitedNot applicableNot applicableCanada
Teva-rosiglitazonetablet8 mgoralTeva Canada LimitedNot applicableNot applicableCanada
Teva-rosiglitazonetablet4 mgoralTeva Canada LimitedNot applicableNot applicableCanada
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-rosiglitazonetablet2.0 mgoralApotex IncNot applicableNot applicableCanada
Apo-rosiglitazonetablet8.0 mgoralApotex IncNot applicableNot applicableCanada
Apo-rosiglitazonetablet4.0 mgoralApotex IncNot applicableNot applicableCanada
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
BlutabWerrick
DH-RosidiaHasan
DiabenElea
DiaglinexFarmindustria
GaudilCraveri
GliximinaDenver
NaidiHisun
RogelinTorrent
RoglitGedeon Richter
RomerolDrug International
RositDelta
RosixGarmisch
RossiniTrima
SensulinSquare
Sheng AoHengrui
Sheng MinShengJiTang Pharmaceutical
Brand mixtures
NameLabellerIngredients
AvandametGlaxo Smith Kline Llc
AvandarylGlaxo Smith Kline Llc
PMS-rosiglitazone-metforminPharmascience Inc
Salts
Name/CASStructureProperties
Rosiglitazone Maleate
155141-29-0
Thumb
  • InChI Key: SUFUKZSWUHZXAV-BTJKTKAUNA-N
  • Monoisotopic Mass: 473.125670795
  • Average Mass: 473.499
DBSALT000153
Categories
UNII05V02F2KDG
CAS number122320-73-4
WeightAverage: 357.427
Monoisotopic: 357.114712179
Chemical FormulaC18H19N3O3S
InChI KeyInChIKey=YASAKCUCGLMORW-UHFFFAOYNA-N
InChI
InChI=1/C18H19N3O3S/c1-21(16-4-2-3-9-19-16)10-11-24-14-7-5-13(6-8-14)12-15-17(22)20-18(23)25-15/h2-9,15H,10-12H2,1H3,(H,20,22,23)
IUPAC Name
5-[(4-{2-[methyl(pyridin-2-yl)amino]ethoxy}phenyl)methyl]-1,3-thiazolidine-2,4-dione
SMILES
CN(CCOC1=CC=C(CC2SC(=O)NC2=O)C=C1)C1=CC=CC=N1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as phenol ethers. These are aromatic compounds containing an ether group substituted with a benzene ring.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassPhenol ethers
Direct ParentPhenol ethers
Alternative Parents
Substituents
  • Dialkylarylamine
  • Phenol ether
  • Thiazolidinedione
  • Aminopyridine
  • Alkyl aryl ether
  • Imidolactam
  • Pyridine
  • Heteroaromatic compound
  • Thiazolidine
  • Tertiary amine
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Thioether
  • Ether
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationRosiglitazone is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
PharmacodynamicsWhen rosiglitazone is used as monotherapy, it is associated with increases in total cholesterol, LDL, and HDL. It is also associated with decreases in free fatty acids. Increases in LDL occurred primarily during the first 1 to 2 months of therapy with AVANDIA and LDL levels remained elevated above baseline throughout the trials. In contrast, HDL continued to rise over time. As a result, the LDL/HDL ratio peaked after 2 months of therapy and then appeared to decrease over time.
Mechanism of actionRosiglitazone acts as a highly selective and potent agonist at peroxisome proliferator activated receptors (PPAR) in target tissues for insulin action such as adipose tissue, skeletal muscle, and liver. Activation of PPAR-gamma receptors regulates the transcription of insulin-responsive genes involved in the control of glucose production, transport, and utilization. In this way, rosiglitazone enhances tissue sensitivity to insulin.
Related Articles
AbsorptionThe absolute bioavailability of rosiglitazone is 99%. Peak plasma concentrations are observed about 1 hour after dosing. Administration of rosiglitazone with food resulted in no change in overall exposure (AUC), but there was an approximately 28% decrease in Cmax and a delay in Tmax (1.75 hours). These changes are not likely to be clinically significant; therefore, rosiglitazone may be administered with or without food. Maximum plasma concentration (Cmax) and the area under the curve (AUC) of rosiglitazone increase in a dose-proportional manner over the therapeutic dose range.
Volume of distribution
  • 17.6 L [oral volume of distribution Vss/F]
  • 13.5 L [population mean, pediatric patients]
Protein binding99.8% bound to plasma proteins, primarily albumin.
Metabolism

Hepatic. Rosiglitazone is extensively metabolized in the liver to inactive metabolites via N-demethylation, hydroxylation, and conjugation with sulfate and glucuronic acid. In vitro data have shown that Cytochrome (CYP) P450 isoenzyme 2C8 (CYP2C8) and to a minor extent CYP2C9 are involved in the hepatic metabolism of rosiglitazone.

SubstrateEnzymesProduct
Rosiglitazone
N-DesmethylrosiglitazoneDetails
Rosiglitazone
para-HydroxyrosiglitazoneDetails
Rosiglitazone
ortho-HydroxyrosiglitazoneDetails
Rosiglitazone
Not Available
N-Despyridinyl rosiglitazoneDetails
N-Desmethylrosiglitazone
Not Available
N-Desmethyl-ortho-hydroxy rosiglitazoneDetails
ortho-Hydroxyrosiglitazone
Not Available
N-Desmethyl-ortho-hydroxy rosiglitazoneDetails
N-Desmethylrosiglitazone
Not Available
N-Desmethyl-para-hydroxy rosiglitazoneDetails
para-Hydroxyrosiglitazone
Not Available
N-Desmethyl-para-hydroxy rosiglitazoneDetails
N-Desmethyl-ortho-hydroxy rosiglitazone
Not Available
N-Desmethyl-ortho-O-sulfate rosiglitazoneDetails
ortho-Hydroxyrosiglitazone
Not Available
ortho-O-Glucuronide rosiglitazoneDetails
ortho-Hydroxyrosiglitazone
Not Available
ortho-O-Sulfate rosiglitazoneDetails
N-Desmethylrosiglitazone
Not Available
N-Desmethyl glucuronide rosiglitazoneDetails
para-Hydroxyrosiglitazone
Not Available
para-O-Glucuronide rosiglitazoneDetails
para-Hydroxyrosiglitazone
Not Available
para-O-Sulfate rosiglitazoneDetails
N-Desmethyl-para-hydroxy rosiglitazone
Not Available
N-Desmethyl para-O-sulfate rosiglitazoneDetails
Rosiglitazone
Not Available
Phenoxyacetic acid derivative of rosiglitazoneDetails
Route of eliminationFollowing oral or intravenous administration of [14C]rosiglitazone maleate, approximately 64% and 23% of the dose was eliminated in the urine and in the feces, respectively.
Half life3-4 hours (single oral dose, independent of dose)
Clearance
  • Oral clearance (CL) = 3.03 ± 0.87 L/hr [1 mg Fasting]
  • Oral CL = 2.89 ± 0.71 L/hr [2 mg Fasting]
  • Oral CL = 2.85 ± 0.69 L/hr [8 mg Fasting]
  • Oral CL = 2.97 ± 0.81 L/hr [8 mg Fed]
  • 3.15 L/hr [Population mean, Pediatric patients]
ToxicitySide effects include fluid retention, congestive heart failure (CHF), liver disease
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Rosiglitazone Metabolism PathwayDrug metabolismSMP00653
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9861
Blood Brain Barrier+0.8994
Caco-2 permeable-0.5451
P-glycoprotein substrateSubstrate0.6535
P-glycoprotein inhibitor INon-inhibitor0.5274
P-glycoprotein inhibitor IINon-inhibitor0.6289
Renal organic cation transporterNon-inhibitor0.5203
CYP450 2C9 substrateNon-substrate0.7418
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.5744
CYP450 1A2 substrateInhibitor0.5391
CYP450 2C9 inhibitorInhibitor0.5783
CYP450 2D6 inhibitorNon-inhibitor0.846
CYP450 2C19 inhibitorInhibitor0.5884
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7213
Ames testNon AMES toxic0.687
CarcinogenicityNon-carcinogens0.9465
BiodegradationNot ready biodegradable0.8635
Rat acute toxicity2.4515 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8055
hERG inhibition (predictor II)Non-inhibitor0.7768
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Sb pharmco puerto rico inc
  • Glaxosmithkline
Packagers
Dosage forms
FormRouteStrength
Tabletoral2.0 mg
Tabletoral4.0 mg
Tabletoral8.0 mg
Tabletoral
Tablet, film coatedoral
Tabletoral2 mg
Tabletoral4 mg
Tabletoral8 mg
Tablet, film coatedoral2 mg/1
Tablet, film coatedoral8 mg/1
Tablet, film coatedoral4 mg/1
Prices
Unit descriptionCostUnit
Avandia 8 mg tablet8.69USD tablet
Avandia 4 mg tablet4.72USD tablet
Avandia 2 mg tablet3.22USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA1328452 No1994-04-122011-04-12Canada
CA2143849 No2000-04-252013-09-01Canada
US5002953 No1994-09-172011-09-17Us
US5965584 No1996-06-192016-06-19Us
US6166042 No1996-06-192016-06-19Us
US6288095 Yes1997-08-112017-08-11Us
US7358366 Yes2000-10-192020-10-19Us
US8236345 No2002-10-072022-10-07Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point122-123 °CNot Available
logP2.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.038 mg/mLALOGPS
logP2.95ALOGPS
logP2.45ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)6.84ChemAxon
pKa (Strongest Basic)6.23ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area71.53 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity97.79 m3·mol-1ChemAxon
Polarizability37.8 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

Manne Reddy, “Amorphous form of rosiglitazone maleate and process for preparation thereof.” U.S. Patent US20040242658, issued December 02, 2004.

US20040242658
General References
  1. Mohanty P, Aljada A, Ghanim H, Hofmeyer D, Tripathy D, Syed T, Al-Haddad W, Dhindsa S, Dandona P: Evidence for a potent antiinflammatory effect of rosiglitazone. J Clin Endocrinol Metab. 2004 Jun;89(6):2728-35. [PubMed:15181049 ]
  2. Kahn SE, Haffner SM, Heise MA, Herman WH, Holman RR, Jones NP, Kravitz BG, Lachin JM, O'Neill MC, Zinman B, Viberti G: Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med. 2006 Dec 7;355(23):2427-43. Epub 2006 Dec 4. [PubMed:17145742 ]
External Links
ATC CodesA10BD03A10BD04A10BG02
AHFS Codes
  • 68:20.28
PDB EntriesNot Available
FDA labelDownload (86.2 KB)
MSDSDownload (30 KB)
Interactions
Drug Interactions
Drug
AbirateroneThe serum concentration of Rosiglitazone can be increased when it is combined with Abiraterone.
Acetylsalicylic acidAcetylsalicylic acid may increase the hypoglycemic activities of Rosiglitazone.
AmiodaroneThe metabolism of Amiodarone can be decreased when combined with Rosiglitazone.
AmodiaquineThe serum concentration of Amodiaquine can be increased when it is combined with Rosiglitazone.
AtazanavirThe serum concentration of Rosiglitazone can be increased when it is combined with Atazanavir.
ChlorpropamideRosiglitazone may increase the hypoglycemic activities of Chlorpropamide.
CholestyramineThe serum concentration of Rosiglitazone can be decreased when it is combined with Cholestyramine.
DabrafenibThe serum concentration of Rosiglitazone can be decreased when it is combined with Dabrafenib.
DeferasiroxThe serum concentration of Rosiglitazone can be increased when it is combined with Deferasirox.
DihydrotestosteroneDihydrotestosterone may increase the hypoglycemic activities of Rosiglitazone.
EnzalutamideThe metabolism of Enzalutamide can be decreased when combined with Rosiglitazone.
Erythrityl TetranitrateThe risk or severity of adverse effects can be increased when Erythrityl Tetranitrate is combined with Rosiglitazone.
GemfibrozilThe metabolism of Rosiglitazone can be decreased when combined with Gemfibrozil.
Insulin AspartThe risk or severity of adverse effects can be increased when Insulin Aspart is combined with Rosiglitazone.
Insulin DegludecThe risk or severity of adverse effects can be increased when Insulin degludec is combined with Rosiglitazone.
Insulin DetemirThe risk or severity of adverse effects can be increased when Insulin Detemir is combined with Rosiglitazone.
Insulin GlargineThe risk or severity of adverse effects can be increased when Insulin Glargine is combined with Rosiglitazone.
Insulin GlulisineThe risk or severity of adverse effects can be increased when Insulin Glulisine is combined with Rosiglitazone.
Insulin HumanThe risk or severity of adverse effects can be increased when Insulin Regular is combined with Rosiglitazone.
Insulin LisproThe risk or severity of adverse effects can be increased when Insulin Lispro is combined with Rosiglitazone.
IsosorbideThe risk or severity of adverse effects can be increased when Isosorbide is combined with Rosiglitazone.
Isosorbide DinitrateThe risk or severity of adverse effects can be increased when Isosorbide Dinitrate is combined with Rosiglitazone.
Isosorbide MononitrateThe risk or severity of adverse effects can be increased when Isosorbide Mononitrate is combined with Rosiglitazone.
LeuprolideThe therapeutic efficacy of Rosiglitazone can be decreased when used in combination with Leuprolide.
Lipoic AcidLipoic Acid may increase the hypoglycemic activities of Rosiglitazone.
LumacaftorThe serum concentration of Rosiglitazone can be increased when it is combined with Lumacaftor.
MifepristoneThe serum concentration of Rosiglitazone can be increased when it is combined with Mifepristone.
NitroglycerinThe risk or severity of adverse effects can be increased when Nitroglycerin is combined with Rosiglitazone.
OxandroloneOxandrolone may increase the hypoglycemic activities of Rosiglitazone.
PaclitaxelThe metabolism of Paclitaxel can be decreased when combined with Rosiglitazone.
ParoxetineParoxetine may increase the hypoglycemic activities of Rosiglitazone.
PegvisomantPegvisomant may increase the hypoglycemic activities of Rosiglitazone.
PhenelzinePhenelzine may increase the hypoglycemic activities of Rosiglitazone.
PhenytoinThe metabolism of Rosiglitazone can be increased when combined with Phenytoin.
PioglitazoneThe metabolism of Pioglitazone can be decreased when combined with Rosiglitazone.
PregabalinPregabalin may increase the fluid retaining activities of Rosiglitazone.
RepaglinideThe metabolism of Repaglinide can be decreased when combined with Rosiglitazone.
RifampicinThe metabolism of Rosiglitazone can be increased when combined with Rifampicin.
RitonavirThe metabolism of Rosiglitazone can be decreased when combined with Ritonavir.
SparfloxacinSparfloxacin may increase the hypoglycemic activities of Rosiglitazone.
TestosteroneTestosterone may increase the hypoglycemic activities of Rosiglitazone.
TorasemideThe metabolism of Torasemide can be decreased when combined with Rosiglitazone.
TranylcypromineTranylcypromine may increase the hypoglycemic activities of Rosiglitazone.
TretinoinThe metabolism of Tretinoin can be decreased when combined with Rosiglitazone.
TrichlormethiazideThe therapeutic efficacy of Rosiglitazone can be decreased when used in combination with Trichlormethiazide.
TrimethoprimThe metabolism of Rosiglitazone can be decreased when combined with Trimethoprim.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
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) and modulates the transcription of its target genes, such as acyl-CoA oxidase. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation...
Gene Name:
PPARG
Uniprot ID:
P37231
Molecular Weight:
57619.58 Da
References
  1. Su JL, Winegar DA, Wisely GB, Sigel CS, Hull-Ryde EA: Use of a PPAR gamma-specific monoclonal antibody to demonstrate thiazolidinediones induce PPAR gamma receptor expression in vitro. Hybridoma. 1999 Jun;18(3):273-80. [PubMed:10475242 ]
  2. Rieusset J, Auwerx J, Vidal H: Regulation of gene expression by activation of the peroxisome proliferator-activated receptor gamma with rosiglitazone (BRL 49653) in human adipocytes. Biochem Biophys Res Commun. 1999 Nov;265(1):265-71. [PubMed:10548525 ]
  3. Kameda N, Okuya S, Oka Y: [Rosiglitazone (BRL-49653)]. Nihon Rinsho. 2000 Feb;58(2):401-4. [PubMed:10707565 ]
  4. Johnson BA, Wilson EM, Li Y, Moller DE, Smith RG, Zhou G: Ligand-induced stabilization of PPARgamma monitored by NMR spectroscopy: implications for nuclear receptor activation. J Mol Biol. 2000 Apr 28;298(2):187-94. [PubMed:10764590 ]
  5. Camp HS, Li O, Wise SC, Hong YH, Frankowski CL, Shen X, Vanbogelen R, Leff T: Differential activation of peroxisome proliferator-activated receptor-gamma by troglitazone and rosiglitazone. Diabetes. 2000 Apr;49(4):539-47. [PubMed:10871190 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Very long-chain fatty acid-coa ligase activity
Specific Function:
Activation of long-chain fatty acids for both synthesis of cellular lipids, and degradation via beta-oxidation. Preferentially uses arachidonate and eicosapentaenoate as substrates.
Gene Name:
ACSL4
Uniprot ID:
O60488
Molecular Weight:
79187.38 Da
References
  1. Askari B, Kanter JE, Sherrid AM, Golej DL, Bender AT, Liu J, Hsueh WA, Beavo JA, Coleman RA, Bornfeldt KE: Rosiglitazone inhibits acyl-CoA synthetase activity and fatty acid partitioning to diacylglycerol and triacylglycerol via a peroxisome proliferator-activated receptor-gamma-independent mechanism in human arterial smooth muscle cells and macrophages. Diabetes. 2007 Apr;56(4):1143-52. Epub 2007 Jan 26. [PubMed:17259370 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
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 unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme...
Gene Name:
CYP2C8
Uniprot ID:
P10632
Molecular Weight:
55824.275 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
substrateinhibitor
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 unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenyto...
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular Weight:
55627.365 Da
References
  1. 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 ]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
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 gastric epithelial cells, it is a key step in the generation of prostaglandins, such as prostaglandin E2 (PGE2), which plays an important role in cytoprotection. In platelets, it is involved in the gener...
Gene Name:
PTGS1
Uniprot ID:
P23219
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. [PubMed:19515014 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
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 unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N...
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular Weight:
58293.76 Da
References
  1. 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
inhibitor
General Function:
Steroid hydroxylase activity
Specific Function:
Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Constitutes the major nicotine C-oxidase. Acts as a 1,4-cineole 2-exo-monooxygenase. Possesses low phenacetin O-deethylation activity.
Gene Name:
CYP2A6
Uniprot ID:
P11509
Molecular Weight:
56501.005 Da
References
  1. 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
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 imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular Weight:
55930.545 Da
References
  1. 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
inhibitor
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular Weight:
55768.94 Da
References
  1. 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 ]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
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 colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds about 80% of all plasma zinc.
Gene Name:
ALB
Uniprot ID:
P02768
Molecular Weight:
69365.94 Da

Transporters

Kind
Protein
Organism
Human
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, prostaglandin E2, thromboxane B2, leukotriene C3, leukotriene E4, thyroxine and triiodothyronine. Involved in the clearance of bile acids and organic anions from the liver.
Gene Name:
SLCO1B1
Uniprot ID:
Q9Y6L6
Molecular Weight:
76447.99 Da
References
  1. Nozawa T, Sugiura S, Nakajima M, Goto A, Yokoi T, Nezu J, Tsuji A, Tamai I: Involvement of organic anion transporting polypeptides in the transport of troglitazone sulfate: implications for understanding troglitazone hepatotoxicity. Drug Metab Dispos. 2004 Mar;32(3):291-4. [PubMed:14977862 ]
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Drug created on June 13, 2005 07:24 / Updated on June 29, 2016 03:04