Human Metabolome Database Version 3.5

Showing metabocard for Atorvastatin (HMDB05006)

Record Information
Version 3.5
Creation Date 2006-10-16 06:25:20 -0600
Update Date 2013-03-26 14:20:55 -0600
HMDB ID HMDB05006
Secondary Accession Numbers None
Metabolite Identification
Common Name Atorvastatin
Description Atorvastatin is a member of the drug class known as statins, used for lowering cholesterol and thereby reducing cardiovascular disease. Atorvastatin inhibits a rate-determining enzyme located in hepatic tissue used in cholesterol synthesis, which lowers the amount of cholesterol produced. This also has the effect of lowering the total amount of LDL cholesterol; Atorvastatin is a member of the drug class known as statins, used for lowering cholesterol and thereby reducing cardiovascular disease. Atorvastatin inhibits a rate-determining enzyme located in hepatic tissue used in cholesterol synthesis, which lowers the amount of cholesterol produced. This also has the effect of lowering the total amount of LDL cholesterol; As with other statins, atorvastatin is a competitive inhibitor of HMG-CoA reductase. Unlike most others, however, it is a completely synthetic compound. HMG-CoA reductase catalyzes the reduction of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) to mevalonate, which is the rate-limiting step in hepatic cholesterol biosynthesis. Inhibition of the enzyme decreases de novo cholesterol synthesis, increasing expression of low-density lipoprotein receptors (LDL receptors) on hepatocytes. This increases the LDL uptake by the hepatocytes, decreasing the amount of LDL in the blood.
Structure Thumb
Download: MOL | SDF | PDB | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  1. Atorvastatin acid
  2. Atorvastatin calcium
  3. Cardyl
  4. Lipitor
Chemical Formula C33H35FN2O5
Average Molecular Weight 558.6398
Monoisotopic Molecular Weight 558.253000445
IUPAC Name (3R,5R)-7-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-(propan-2-yl)-1H-pyrrol-1-yl]-3,5-dihydroxyheptanoic acid
Traditional IUPAC Name atorvastatin
CAS Registry Number 134523-00-5
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
InChI Identifier 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
InChI Key XUKUURHRXDUEBC-KAYWLYCHSA-N
Chemical Taxonomy
Kingdom Organic Compounds
Super Class Aromatic Heteropolycyclic Compounds
Class Anilides
Sub Class N/A
Other Descriptors
  • Aromatic Heteropolycyclic Compounds
  • Branched Fatty Acids
  • Halogenated Fatty Acids
  • Heterocyclic Fatty Acids
  • Organic Compounds
  • dihydroxy monocarboxylic acid(ChEBI)
  • pyrroles(ChEBI)
Substituents
  • Aryl Fluoride
  • Beta Hydroxy Acid
  • Carboxamide Group
  • Carboxylic Acid
  • Fluorobenzene
  • Organofluoride
  • Pyrrole
  • Secondary Alcohol
  • Secondary Carboxylic Acid Amide
Direct Parent Anilides
Ontology
Status Detected and Quantified
Origin
  • Endogenous
Biofunction Not Available
Application Not Available
Cellular locations
  • Membrane (predicted from logP)
Physical Properties
State Solid
Experimental Properties
Property Value Reference
Melting Point 159.1 - 190.6 °C Not Available
Boiling Point Not Available Not Available
Water Solubility Not Available Not Available
LogP Not Available Not Available
Predicted Properties
Property Value Source
Water Solubility 6.300E-04 g/L ALOGPS
LogP 4.24 ALOGPS
LogP 5.39 ChemAxon
LogS -5.95 ALOGPS
pKa (strongest acidic) 4.33 ChemAxon
pKa (strongest basic) -2.7 ChemAxon
Hydrogen Acceptor Count 5 ChemAxon
Hydrogen Donor Count 4 ChemAxon
Polar Surface Area 111.79 A2 ChemAxon
Rotatable Bond Count 12 ChemAxon
Refractivity 158.2 ChemAxon
Polarizability 59.39 ChemAxon
Formal Charge 0 ChemAxon
Physiological Charge -1 ChemAxon
Spectra
Not Available
Biological Properties
Cellular Locations
  • Membrane (predicted from logP)
Biofluid Locations
  • Blood
Tissue Location
  • Liver
  • Platelet
Pathways Not Available
Normal Concentrations
Biofluid Status Value Age Sex Condition Reference
Blood Detected and Quantified
0.010 +/- 0.0044 uM Adult (>18 years old) Both Normal
Abnormal Concentrations
Biofluid Status Value Age Sex Condition Reference
Blood Detected and Quantified 0.22 +/- 0.16 uM Adult (>18 years old) Both Sepsis patients dosed with 20 mg of Atorvastatin
Associated Disorders and Diseases
Disease References
Sepsis
  • Kruger PS, Freir NM, Venkatesh B, Robertson TA, Roberts MS, Jones M: A preliminary study of atorvastatin plasma concentrations in critically ill patients with sepsis. Intensive Care Med. 2008 Nov 26. Pubmed: 19034423 Link_out
      Associated OMIM IDs None
      DrugBank ID Not Available
      DrugBank Metabolite ID Not Available
      Phenol Explorer Compound ID Not Available
      Phenol Explorer Metabolite ID Not Available
      FoodDB ID FDB023579
      KNApSAcK ID Not Available
      Chemspider ID 54810 Link_out
      KEGG Compound ID C06834 Link_out
      BioCyc ID Not Available
      BiGG ID Not Available
      Wikipedia Link Atorvastatin Link_out
      NuGOwiki Link HMDB05006 Link_out
      Metagene Link HMDB05006 Link_out
      METLIN ID 1136 Link_out
      PubChem Compound 60823 Link_out
      PDB ID 117 Link_out
      ChEBI ID 2910 Link_out
      References
      Synthesis Reference Roth, Bruce David. Preparation of anticholesteremic (R-(R*R*))-2-(4-fluorophenyl)-b, d-dihydroxy-5-(1-methylethyl-3-phenyl-4((phenylamino)carbonyl)-1H-pyrrolyl-1-heptanoic acid, its lactone form and salts thereof. Eur. Pat. Appl. (1991), 18 pp. CODEN: EPXXDW EP 409281 A1 19910123 CAN 115:29107 AN 1991:429107
      Material Safety Data Sheet (MSDS) Not Available
      General References
      1. Taylor PJ, Kubler PA, Lynch SV, Allen J, Butler M, Pillans PI: Effect of atorvastatin on cyclosporine pharmacokinetics in liver transplant recipients. Ann Pharmacother. 2004 Feb;38(2):205-8. Epub 2003 Dec 19. Pubmed: 14742751 Link_out
      2. Funatsu T, Suzuki K, Goto M, Arai Y, Kakuta H, Tanaka H, Yasuda S, Ida M, Nishijima S, Miyata K: Prolonged inhibition of cholesterol synthesis by atorvastatin inhibits apo B-100 and triglyceride secretion from HepG2 cells. Atherosclerosis. 2001 Jul;157(1):107-15. Pubmed: 11427209 Link_out
      3. Tannous M, Cheung R, Vignini A, Mutus B: Atorvastatin increases ecNOS levels in human platelets of hyperlipidemic subjects. Thromb Haemost. 1999 Nov;82(5):1390-4. Pubmed: 10595624 Link_out
      4. Naoumova RP, Dunn S, Rallidis L, Abu-Muhana O, Neuwirth C, Rendell NB, Taylor GW, Thompson GR: Prolonged inhibition of cholesterol synthesis explains the efficacy of atorvastatin. J Lipid Res. 1997 Jul;38(7):1496-500. Pubmed: 9254075 Link_out
      5. Izar MC: [Hypolipidemic treatment under special conditions: posttransplant and/or immunosuppressive therapy] Arq Bras Cardiol. 2005 Oct;85 Suppl 5:50-7. Epub 2006 Jan 2. Pubmed: 16400400 Link_out
      6. Hwang YS, Tsai WC, Lu YH, Lin CC, Chen YF: Effect of atorvastatin on the expression of CD40 ligand and P-selectin on platelets in patients with hypercholesterolemia. Am J Cardiol. 2004 Aug 1;94(3):364-6. Pubmed: 15276107 Link_out
      7. Bruni F, Pasqui AL, Pastorelli M, Bova G, Cercignani M, Palazzuoli A, Sawamura T, Auteri A, Puccetti L: Different effect of statins on platelet oxidized-LDL receptor (CD36 and LOX-1) expression in hypercholesterolemic subjects. Clin Appl Thromb Hemost. 2005 Oct;11(4):417-28. Pubmed: 16244767 Link_out
      8. Fenton JW 2nd, Brezniak DV, Ofosu FA, Shen GX, Jacobson JR, Garcia JG: Statins and thrombin. Curr Drug Targets Cardiovasc Haematol Disord. 2005 Apr;5(2):115-20. Pubmed: 15853752 Link_out
      9. Pokrovskaia EV, Vaulin NA, Gratsianskii NA, Averkov OV, Deev AD: [Markers of inflammation and platelet aggregation in patients with non ST elevation acute coronary syndrome treated with atorvastatin or pravastatin] Kardiologiia. 2003;43(1):7-18. Pubmed: 12891281 Link_out
      10. Funatsu T, Kakuta H, Tanaka H, Arai Y, Suzuki K, Miyata K: [Atorvastatin (Lipitor): a review of its pharmacological and clinical profile] Nippon Yakurigaku Zasshi. 2001 Jan;117(1):65-76. Pubmed: 11233299 Link_out
      11. Tousoulis D, Bosinakou E, Kotsopoulou M, Antoniades C, Katsi V, Stefanadis C: Effects of early administration of atorvastatin treatment on thrombotic process in normocholesterolemic patients with unstable angina. Int J Cardiol. 2006 Jan 26;106(3):333-7. Pubmed: 16337041 Link_out
      12. Malinowski JM: Atorvastatin: a hydroxymethylglutaryl-coenzyme A reductase inhibitor. Am J Health Syst Pharm. 1998 Nov 1;55(21):2253-67; quiz 2302-3. Pubmed: 9825877 Link_out

      Enzymes
      Name: Serum paraoxonase/arylesterase 1
      Reactions: Not Available
      Gene Name: PON1
      Uniprot ID: P27169 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      Name: 3-hydroxy-3-methylglutaryl-coenzyme A reductase
      Reactions: Not Available
      Gene Name: HMGCR
      Uniprot ID: P04035 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      Name: Cytochrome P450 3A4
      Reactions: Not Available
      Gene Name: CYP3A4
      Uniprot ID: P08684 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      Name: Plasminogen activator inhibitor 1
      Reactions: Not Available
      Gene Name: SERPINE1
      Uniprot ID: P05121 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      Name: C-C motif chemokine 2
      Reactions: Not Available
      Gene Name: CCL2
      Uniprot ID: P13500 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      Name: Transforming protein RhoA
      Reactions: Not Available
      Gene Name: RHOA
      Uniprot ID: P61586 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      Name: Tumor necrosis factor
      Reactions: Not Available
      Gene Name: TNF
      Uniprot ID: P01375 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      Name: C-reactive protein
      Reactions: Not Available
      Gene Name: CRP
      Uniprot ID: P02741 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      Name: Apolipoprotein B-100
      Reactions: Not Available
      Gene Name: APOB
      Uniprot ID: P04114 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      Name: Vascular endothelial growth factor A
      Reactions: Not Available
      Gene Name: VEGFA
      Uniprot ID: P15692 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      Name: CD40 ligand
      Reactions: Not Available
      Gene Name: CD40LG
      Uniprot ID: P29965 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      Name: Peroxisome proliferator-activated receptor gamma
      Reactions: Not Available
      Gene Name: PPARG
      Uniprot ID: P37231 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      Name: Peroxisome proliferator-activated receptor alpha
      Reactions: Not Available
      Gene Name: PPARA
      Uniprot ID: Q07869 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      Name: Angiotensinogen
      Reactions: Not Available
      Gene Name: AGT
      Uniprot ID: P01019 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      Name: Collagen alpha-1(XIII) chain
      Reactions: Not Available
      Gene Name: COL13A1
      Uniprot ID: Q5TAT6 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      Name: DNA replication licensing factor MCM6
      Reactions: Not Available
      Gene Name: MCM6
      Uniprot ID: Q14566 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      Name: DNA replication licensing factor MCM7
      Reactions: Not Available
      Gene Name: MCM7
      Uniprot ID: P33993 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA