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Identification
Name Atorvastatin
Accession Number DB01076 (APRD00055)
Type small molecule
Groups approved
Description

Atorvastatin (Lipitor) is a member of the drug class known as statins. It is used for lowering cholesterol. Atorvastatin is a competitive inhibitor of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase, the rate-determining enzyme in cholesterol biosynthesis via the mevalonate pathway. HMG-CoA reductase catalyzes the conversion of HMG-CoA to mevalonate. Atorvastatin acts primarily in the liver. Decreased hepatic cholesterol levels increases hepatic uptake of cholesterol and reduces plasma cholesterol levels.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Atorvastatin calcium
Brand names
  • Atogal (Ingers (Czech Republic))
  • Atorpic
  • Cardyl (Pfizer (Spain))
  • Faboxim (Fabop (Argentina))
  • Hipolixan (Pasteur (Chile))
  • Lipitor (Pfizer, Elea (Argentina))
  • Lipotropic (Drugtech (Chile))
  • Lipovastatinklonal (Klonal (Argentina))
  • Liprimar (Pfizer (Hungary, Ukraine), Goedecke (Russia))
  • Lowden (Saval (Chile))
  • Normalip (Quesada (Argentina))
  • Sincol (Indeco (Argentina))
  • Sortis (Pfizer (Austria, Czech Republic, Germany, Hungary, Poland, Portugal, Switzerland), Godecke (Germany), Parke, Davis (Germany))
  • Sotis
  • Torvacard (Zentiva (Czech Republic, Hungary, Poland, Russia, Ukraine))
  • Torvast (Pfizer (Italy))
  • Totalip (Guidotti (Italy))
  • Tozalip
  • Tulip (Lek (Czech Republic, Russia), Wermar (Mexico), Sandoz (Poland, Ukraine), Pharmacia (Spain))
  • Vastina (Penn (Argentina))
  • Xanator (Sieger (Greece))
  • Xarator (Parke, Davis (Italy))
  • Xavator
  • Zurinel (Prater (Chile))
Brand name mixtures
  • Caduet (atorvastatin calcium, amlodipine besilate)
Categories
  • Anticholesteremic Agents
  • HMG-CoA Reductase Inhibitors
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
CAS number 134523-00-5
Weight Average: 558.6398
Monoisotopic: 558.253000445
Chemical Formula C33H35FN2O5
InChI Key InChIKey=XUKUURHRXDUEBC-KAYWLYCHSA-N
InChI
InChI=1S/C33H35FN2O5/c1-21(2)31-30(33(41)35-25-11-7-4-8-12-25)29(22-9-5-3-6-10-22)32(23-13-15-24(34)16-14-23)36(31)18-17-26(37)19-27(38)20-28(39)40/h3-16,21,26-27,37-38H,17-20H2,1-2H3,(H,35,41)(H,39,40)/t26-,27-/m1/s1
Plain Text
IUPAC Name
(3R,5R)-7-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-(propan-2-yl)-1H-pyrrol-1-yl]-3,5-dihydroxyheptanoic acid
SMILES
CC(C)C1=C(C(=O)NC2=CC=CC=C2)C(=C(N1CC[C@@H](O)C[C@@H](O)CC(O)=O)C1=CC=C(F)C=C1)C1=CC=CC=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Statins
Substructures
  • Statins
  • Hydroxy Compounds
  • Acetates
  • Amino Ketones
  • Phenylpropenes
  • Pyrroles
  • Benzene and Derivatives
  • Carboxylic Acids and Derivatives
  • Halobenzenes
  • Heterocyclic compounds
  • Aromatic compounds
  • Cinnamaldehydes
  • Carboxamides and Derivatives
  • Imines
  • Alcohols and Polyols
  • Aryl Halides
  • Anilines
Pharmacology
Indication May be used as primary prevention in individuals with multiple risk factors for coronary heart disease (CHD) and as secondary prevention in individuals with CHD to reduce the risk of myocardial infarction (MI), stroke, angina, and revascularization procedures. May be used to reduce the risk of cardiovascular events in patients with acute coronary syndrome (ACS). May be used in the treatment of primary hypercholesterolemia and mixed dyslipidemia, homozygous familial hypercholesterolemia, primary dysbetalipoproteinemia, and/or hypertriglyeridemia as an adjunct to dietary therapy to decrease serum total and low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (apoB), and triglyceride concentrations, while increasing high-density lipoprotein cholesterol (HDL-C) levels.
Pharmacodynamics Atorvastatin, a selective, competitive HMG-CoA reductase inhibitor, is used to lower serum total and LDL cholesterol, apoB, and triglyceride levels while increasing HDL cholesterol. High LDL-C, low HDL-C and high TG concentrations in the plasma are associated with increased risk of atherosclerosis and cardiovascular disease. The total cholesterol to HDL-C ratio is a strong predictor of coronary artery disease and high ratios are associated with higher risk of disease. Increased levels of HDL-C are associated with lower cardiovascular risk. By decreasing LDL-C and TG and increasing HDL-C, atorvastatin reduces the risk of cardiovascular morbidity and mortality. Atorvastatin has a unique structure, long half-life, and hepatic selectivity, explaining its greater LDL-lowering potency compared to other HMG-CoA reductase inhibitors.
Mechanism of action Atorvastatin selectively and competitively inhibits the hepatic enzyme HMG-CoA reductase. As HMG-CoA reductase is responsible for converting HMG-CoA to mevalonate in the cholesterol biosynthesis pathway, this results in a subsequent decrease in hepatic cholesterol levels. Decreased hepatic cholesterol levels stimulates upregulation of hepatic LDL-C receptors which increases hepatic uptake of LDL-C and reduces serum LDL-C concentrations.
Absorption Atorvastatin is rapidly absorbed after oral administration with maximum plasma concentrations achieved in 1 to 2 hours. The absolute bioavailability of atorvastatin (parent drug) is approximately 12% and the systemic availability of HMG-CoA reductase inhibitory activity is approximately 30%. The low systemic bioavailability is due to presystemic clearance by gastrointestinal mucosa and first-pass metabolism in the liver.
Volume of distribution
  • 381 L
Protein binding 98% bound to plasma proteins
Metabolism

Atorvastatin is extensively metabolized to ortho- and parahydroxylated derivatives and various beta-oxidation products. In vitro inhibition of HMG-CoA reductase by ortho- and parahydroxylated metabolites is equivalent to that of atorvastatin. Approximately 70% of circulating inhibitory activity for HMG-CoA reductase is attributed to active metabolites.

Enzyme Metabolite Reaction Km Vmax
Cytochrome P450 3A5 para-hydroxyatorvastatin hydroxylation
Cytochrome P450 3A5 ortho-hydroxyatorvastatin hydroxylation
Cytochrome P450 3A4 para-hydroxyatorvastatin hydroxylation 0 0
Cytochrome P450 3A4 ortho-hydroxyatorvastatin hydroxylation 0 0
Cytochrome P450 2C8 para-hydroxyatorvastatin hydroxylation
Route of elimination Eliminated primarily in bile after hepatic and/or extrahepatic metabolism. Does not appear to undergo significant enterohepatic recirculation. Less than 2% of the orally administered dose is recovered in urine.
Half life 14 hours, but half-life of HMG-CoA inhibitor activity is 20-30 hours due to longer-lived active metabolites
Clearance Not Available
Toxicity Generally well-tolerated. Side effects may include myalgia, constipation, asthenia, abdominal pain, and nausea. Other possible side effects include myotoxicity (myopathy, myositis, rhabdomyolysis) and hepatotoxicity. To avoid toxicity in Asian patients, lower doses should be considered.
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00131 Atorvastatin Pathway SMP00131
Pharmacoeconomics
Manufacturers
  • Pfizer inc
Packagers
Dosage forms
Form Route Strength
Tablet Oral 10 mg
Tablet Oral 20 mg
Tablet Oral 40 mg
Tablet Oral 80 mg
Prices
Unit description Cost Unit
Lipitor 20 mg tablet 5.0 USD tablet
Lipitor 40 mg tablet 5.0 USD tablet
Lipitor 80 mg tablet 5.0 USD tablet
Lipitor 10 mg tablet 3.5 USD tablet
Lipitor 40 mg Tablet 2.52 USD tablet
Lipitor 80 mg Tablet 2.52 USD tablet
Lipitor 20 mg Tablet 2.34 USD tablet
Lipitor 10 mg Tablet 1.87 USD tablet
Patents
Country Patent Number Approved Expires
United States 5969156 1997-01-08 2017-01-08
United States 4681893 1992-09-24 2009-09-24
Canada 2521776 2006-04-25 2022-05-21
Canada 2220018 2001-04-17 2016-07-08
Properties
State solid
Melting point 159.2-160.7 oC
Experimental Properties
Property Value Source
water solubility Sodium salt soluble in water, 20.4 ug/mL (pH 2.1), 1.23 mg/mL (pH 6.0) PhysProp
logP 5.7 PhysProp
Predicted Properties
Property Value Source
water solubility 6.30e-04 g/l ALOGPS
logP 4.24 ALOGPS
logP 5.39 ChemAxon Molconvert
logS -5.95 ALOGPS
pKa 11.82 ChemAxon Molconvert
hydrogen acceptor count 5 ChemAxon Molconvert
hydrogen donor count 4 ChemAxon Molconvert
polar surface area 111.79 ChemAxon Molconvert
rotatable bond count 12 ChemAxon Molconvert
refractivity 158.20 ChemAxon Molconvert
polarizability 59.31 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Rouleau J: Improved outcome after acute coronary syndromes with an intensive versus standard lipid-lowering regimen: results from the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) trial. Am J Med. 2005 Dec;118 Suppl 12A:28-35. Pubmed
  2. Maggon K: Best-selling human medicines 2002-2004. Drug Discov Today. 2005 Jun 1;10(11):739-42. Pubmed
External Links
Resource Link
KEGG Compound C06834 Link_out
PubChem Compound 60823 Link_out
PubChem Substance 46506188 Link_out
ChemSpider 54810 Link_out
BindingDB 22164 Link_out
ChEBI 2910 Link_out
ChEMBL 2910 Link_out
Therapeutic Targets Database DAP000553 Link_out
PharmGKB PA448500 Link_out
HET 117 Link_out
Drug Product Database 2243097 Link_out
RxList http://www.rxlist.com/cgi/generic/atorvastatin.htm Link_out
Drugs.com http://www.drugs.com/atorvastatin.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/lip1230.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Atorvastatin Link_out
ATC Codes
  • C10AA05
AHFS Codes
  • 24:06.08
PDB Entries Not Available
FDA label show (62 KB)
MSDS show (57.4 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Avoid alcohol.
  • Avoid drastic changes in dietary habit.
  • Avoid taking grapefruit or grapefruit juice throughout treatment. Grapefruit can significantly increase serum levels of this product.
  • Food may decrease maximum plasma levels and area under the curve, but this is clinically inconsequential according to the manufacturer.
  • Take with low fat meal.
Targets

1. 3-hydroxy-3-methylglutaryl-coenzyme A reductase

Pharmacological action: yes
Actions: inhibitor

This transmembrane glycoprotein is involved in the control of cholesterol biosynthesis. It is the rate-limiting enzyme of sterol biosynthesis

Organism class: human
UniProt ID: P04035 Link_out
Gene: HMGCR Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Davidson MH: Rosuvastatin: a highly efficacious statin for the treatment of dyslipidaemia. Expert Opin Investig Drugs. 2002 Mar;11(3):125-41. Pubmed
  2. Jafari M, Ebrahimi R, Ahmadi-Kashani M, Balian H, Bashir M: Efficacy of alternate-day dosing versus daily dosing of atorvastatin. J Cardiovasc Pharmacol Ther. 2003 Jun;8(2):123-6. Pubmed
  3. Baxter JD, Webb P, Grover G, Scanlan TS: Selective activation of thyroid hormone signaling pathways by GC-1: a new approach to controlling cholesterol and body weight. Trends Endocrinol Metab. 2004 May-Jun;15(4):154-7. Pubmed
  4. Maejima T, Yamazaki H, Aoki T, Tamaki T, Sato F, Kitahara M, Saito Y: Effect of pitavastatin on apolipoprotein A-I production in HepG2 cell. Biochem Biophys Res Commun. 2004 Nov 12;324(2):835-9. Pubmed
  5. Bosel J, Gandor F, Harms C, Synowitz M, Harms U, Djoufack PC, Megow D, Dirnagl U, Hortnagl H, Fink KB, Endres M: Neuroprotective effects of atorvastatin against glutamate-induced excitotoxicity in primary cortical neurones. J Neurochem. 2005 Mar;92(6):1386-98. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Dipeptidyl peptidase 4

Pharmacological action: no
Actions: inhibitor

Removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini provided that the penultimate residue is proline. Plays a role in T-cell activation

Organism class: human
UniProt ID: P27487 Link_out
Gene: DPP4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Taldone T, Zito SW, Talele TT: Inhibition of dipeptidyl peptidase-IV (DPP-IV) by atorvastatin. Bioorg Med Chem Lett. 2008 Jan 15;18(2):479-84. Pubmed

3. Aryl hydrocarbon receptor

Pharmacological action: unknown
Actions: agonist

Ligand-activated transcriptional activator. Binds to the XRE promoter region of genes it activates. Activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons. Involved in cell-cycle regulation. Likely to play an important role in the development and maturation of many tissues

Organism class: human
UniProt ID: P35869 Link_out
Gene: AHR Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Hu W, Sorrentino C, Denison MS, Kolaja K, Fielden MR: Induction of cyp1a1 is a nonspecific biomarker of aryl hydrocarbon receptor activation: results of large scale screening of pharmaceuticals and toxicants in vivo and in vitro. Mol Pharmacol. 2007 Jun;71(6):1475-86. Epub 2007 Feb 27. Pubmed
Enzymes

1. Cytochrome P450 3A4

Actions: substrate, inhibitor, inducer

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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Neuvonen PJ, Niemi M, Backman JT: Drug interactions with lipid-lowering drugs: mechanisms and clinical relevance. Clin Pharmacol Ther. 2006 Dec;80(6):565-81. Pubmed
  2. Cohen LH, van Leeuwen RE, van Thiel GC, van Pelt JF, Yap SH: Equally potent inhibitors of cholesterol synthesis in human hepatocytes have distinguishable effects on different cytochrome P450 enzymes. Biopharm Drug Dispos. 2000 Dec;21(9):353-64. Pubmed
  3. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  4. 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
  5. 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. Epub 2009 Nov 24. Pubmed
  6. Jacobsen W, Kuhn B, Soldner A, Kirchner G, Sewing KF, Kollman PA, Benet LZ, Christians U: Lactonization is the critical first step in the disposition of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor atorvastatin. Drug Metab Dispos. 2000 Nov;28(11):1369-78. Pubmed

2. Cytochrome P450 3A5

Actions: substrate

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

UniProt ID: P20815 Link_out
Gene: CYP3A5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  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. Pubmed
  3. 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. Epub 2009 Nov 24. Pubmed
  4. Jacobsen W, Kuhn B, Soldner A, Kirchner G, Sewing KF, Kollman PA, Benet LZ, Christians U: Lactonization is the critical first step in the disposition of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor atorvastatin. Drug Metab Dispos. 2000 Nov;28(11):1369-78. Pubmed

3. Cytochrome P450 3A7

Actions: substrate

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

UniProt ID: P24462 Link_out
Gene: CYP3A7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

4. Cytochrome P450 2C8

Actions: substrate, inhibitor

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 responsible for the metabolism the anti- cancer drug paclitaxel (taxol)

UniProt ID: P10632 Link_out
Gene: CYP2C8
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Nov 24. Pubmed
  2. Jacobsen W, Kuhn B, Soldner A, Kirchner G, Sewing KF, Kollman PA, Benet LZ, Christians U: Lactonization is the critical first step in the disposition of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor atorvastatin. Drug Metab Dispos. 2000 Nov;28(11):1369-78. Pubmed

5. Cytochrome P450 2D6

Actions: inhibitor

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

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Cohen LH, van Leeuwen RE, van Thiel GC, van Pelt JF, Yap SH: Equally potent inhibitors of cholesterol synthesis in human hepatocytes have distinguishable effects on different cytochrome P450 enzymes. Biopharm Drug Dispos. 2000 Dec;21(9):353-64. Pubmed

6. Cytochrome P450 2C9

Actions: inhibitor, inducer

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, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Cohen LH, van Leeuwen RE, van Thiel GC, van Pelt JF, Yap SH: Equally potent inhibitors of cholesterol synthesis in human hepatocytes have distinguishable effects on different cytochrome P450 enzymes. Biopharm Drug Dispos. 2000 Dec;21(9):353-64. Pubmed
  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. Pubmed

7. Cytochrome P450 2C19

Actions: inhibitor

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

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Cohen LH, van Leeuwen RE, van Thiel GC, van Pelt JF, Yap SH: Equally potent inhibitors of cholesterol synthesis in human hepatocytes have distinguishable effects on different cytochrome P450 enzymes. Biopharm Drug Dispos. 2000 Dec;21(9):353-64. Pubmed

8. Cytochrome P450 2B6

Actions: inducer

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

UniProt ID: P20813 Link_out
Gene: CYP2B6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Transporters

1. Multidrug resistance protein 1

Actions: inhibitor

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Wang E, Casciano CN, Clement RP, Johnson WW: HMG-CoA reductase inhibitors (statins) characterized as direct inhibitors of P-glycoprotein. Pharm Res. 2001 Jun;18(6):800-6. Pubmed
  2. Sieczkowski E, Lehner C, Ambros PF, Hohenegger M: Double impact on p-glycoprotein by statins enhances doxorubicin cytotoxicity in human neuroblastoma cells. Int J Cancer. 2010 May 1;126(9):2025-35. Pubmed

2. Solute carrier organic anion transporter family member 1A2

Actions: inhibitor

Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity)

UniProt ID: P46721 Link_out
Gene: SLCO1A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Hsiang B, Zhu Y, Wang Z, Wu Y, Sasseville V, Yang WP, Kirchgessner TG: A novel human hepatic organic anion transporting polypeptide (OATP2). Identification of a liver-specific human organic anion transporting polypeptide and identification of rat and human hydroxymethylglutaryl-CoA reductase inhibitor transporters. J Biol Chem. 1999 Dec 24;274(52):37161-8. Pubmed

3. Solute carrier organic anion transporter family member 1B1

Actions: substrate, inhibitor

Mediates the Na(+)-independent transport 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. May play an important role in the clearance of bile acids and organic anions from the liver

UniProt ID: Q9Y6L6 Link_out
Gene: SLCO1B1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Hsiang B, Zhu Y, Wang Z, Wu Y, Sasseville V, Yang WP, Kirchgessner TG: A novel human hepatic organic anion transporting polypeptide (OATP2). Identification of a liver-specific human organic anion transporting polypeptide and identification of rat and human hydroxymethylglutaryl-CoA reductase inhibitor transporters. J Biol Chem. 1999 Dec 24;274(52):37161-8. Pubmed
  2. Kameyama Y, Yamashita K, Kobayashi K, Hosokawa M, Chiba K: Functional characterization of SLCO1B1 (OATP-C) variants, SLCO1B1*5, SLCO1B1*15 and SLCO1B1*15+C1007G, by using transient expression systems of HeLa and HEK293 cells. Pharmacogenet Genomics. 2005 Jul;15(7):513-22. Pubmed

4. Multidrug resistance-associated protein 4

Actions: substrate

May be an organic anion pump relevant to cellular detoxification

UniProt ID: O15439 Link_out
Gene: ABCC4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Knauer MJ, Urquhart BL, Meyer zu Schwabedissen HE, Schwarz UI, Lemke CJ, Leake BF, Kim RB, Tirona RG: Human skeletal muscle drug transporters determine local exposure and toxicity of statins. Circ Res. 2010 Feb 5;106(2):297-306. Epub 2009 Nov 25. Pubmed

5. Multidrug resistance-associated protein 5

Actions: substrate

Acts as a multispecific organic anion pump which can transport nucleotide analogs

UniProt ID: O15440 Link_out
Gene: ABCC5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Knauer MJ, Urquhart BL, Meyer zu Schwabedissen HE, Schwarz UI, Lemke CJ, Leake BF, Kim RB, Tirona RG: Human skeletal muscle drug transporters determine local exposure and toxicity of statins. Circ Res. 2010 Feb 5;106(2):297-306. Epub 2009 Nov 25. Pubmed

6. Multidrug resistance-associated protein 1

Actions: substrate

May participate directly in the active transport of drugs into subcellular organelles or influence drug distribution indirectly. Confers resistance to anticancer drugs. Transports LTC4. May protect milk against xenobiotics

UniProt ID: P33527 Link_out
Gene: ABCC1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Knauer MJ, Urquhart BL, Meyer zu Schwabedissen HE, Schwarz UI, Lemke CJ, Leake BF, Kim RB, Tirona RG: Human skeletal muscle drug transporters determine local exposure and toxicity of statins. Circ Res. 2010 Feb 5;106(2):297-306. Epub 2009 Nov 25. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on October 28, 2011 13:29

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.