Record Information
Version3.6
Creation Date2006-10-16 12:25:20 UTC
Update Date2013-03-26 20:20:55 UTC
HMDB IDHMDB05006
Secondary Accession NumbersNone
Metabolite Identification
Common NameAtorvastatin
DescriptionAtorvastatin 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
Synonyms
  1. Atorvastatin acid
  2. Atorvastatin calcium
  3. Cardyl
  4. Lipitor
Chemical FormulaC33H35FN2O5
Average Molecular Weight558.6398
Monoisotopic Molecular Weight558.253000445
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 Nameatorvastatin
CAS Registry Number134523-00-5
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 KeyXUKUURHRXDUEBC-KAYWLYCHSA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassAromatic Heteropolycyclic Compounds
ClassAnilides
Sub ClassN/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 ParentAnilides
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
BiofunctionNot Available
ApplicationNot Available
Cellular locations
  • Membrane (predicted from logP)
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point159.1 - 190.6 °CNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
water solubility6.300E-04 g/LALOGPS
logP4.24ALOGPS
logP5.39ChemAxon
logS-6ALOGPS
pKa (strongest acidic)4.33ChemAxon
pKa (strongest basic)-2.7ChemAxon
physiological charge-1ChemAxon
hydrogen acceptor count5ChemAxon
hydrogen donor count4ChemAxon
polar surface area111.79ChemAxon
rotatable bond count12ChemAxon
refractivity158.2ChemAxon
polarizability59.39ChemAxon
Spectra
SpectraNot Available
Biological Properties
Cellular Locations
  • Membrane (predicted from logP)
Biofluid Locations
  • Blood
Tissue Location
  • Liver
  • Platelet
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReference
BloodDetected and Quantified0.010 +/- 0.0044 uMAdult (>18 years old)BothNormal
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReference
BloodDetected and Quantified0.22 +/- 0.16 uMAdult (>18 years old)BothSepsis 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
Associated OMIM IDsNone
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB023579
KNApSAcK IDNot Available
Chemspider ID54810
KEGG Compound IDC06834
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkAtorvastatin
NuGOwiki LinkHMDB05006
Metagene LinkHMDB05006
METLIN ID1136
PubChem Compound60823
PDB ID117
ChEBI ID2910
References
Synthesis ReferenceRoth, 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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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

Enzymes

Gene Name:
PON1
Uniprot ID:
P27169
Gene Name:
CYP3A4
Uniprot ID:
P08684
Gene Name:
SERPINE1
Uniprot ID:
P05121
Gene Name:
CCL2
Uniprot ID:
P13500
Gene Name:
RHOA
Uniprot ID:
P61586
Gene Name:
TNF
Uniprot ID:
P01375
Gene Name:
CRP
Uniprot ID:
P02741
Gene Name:
APOB
Uniprot ID:
P04114
Gene Name:
VEGFA
Uniprot ID:
P15692
Gene Name:
CD40LG
Uniprot ID:
P29965
Gene Name:
AGT
Uniprot ID:
P01019
Gene Name:
COL13A1
Uniprot ID:
Q5TAT6