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Identification
Name Enoxaparin
Accession Number DB01225 (APRD00068)
Type small molecule
Groups approved
Description

Enoxaparin is a low molecular weight heparin. Enoxaparin is used to prevent and treat deep vein thrombosis or pulmonary embolism, and is given as a subcutaneous injection. Enoxaparin binds to and accelerates the activity of antithrombin III. By activating antithrombin III, enoxaparin preferentially potentiates the inhibition of coagulation factors Xa and IIa. Factor Xa catalyzes the conversion of prothrombin to thrombin, so enoxaparin’s inhibition of this process results in decreased thrombin and ultimately the prevention of fibrin clot formation. Low molecular weight heparins are less effective at inactivating factor IIa due to their shorter length compared to unfractionated heparin.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • enoxaparin
  • LMWH
  • Low Molecular Weight Heparin
Brand names
  • Clexane
  • Lovenox
  • Lovenox HP
Brand name mixtures Not Available
Categories
  • Anticoagulants
  • Fibrinolytic Agents
  • Heparins
CAS number 9005-49-6
Weight Average: 1134.928
Monoisotopic: 1134.006993818
Chemical Formula C26H42N2O37S5
InChI Key InChIKey=HTTJABKRGRZYRN-UHFFFAOYSA-N
InChI
InChI=1S/C26H42N2O37S5/c1-4(30)27-7-9(31)13(6(56-23(7)39)3-55-67(43,44)45)58-26-19(65-70(52,53)54)12(34)16(20(62-26)22(37)38)60-24-8(28-66(40,41)42)15(63-68(46,47)48)14(5(2-29)57-24)59-25-18(64-69(49,50)51)11(33)10(32)17(61-25)21(35)36/h5-20,23-26,28-29,31-34,39H,2-3H2,1H3,(H,27,30)(H,35,36)(H,37,38)(H,40,41,42)(H,43,44,45)(H,46,47,48)(H,49,50,51)(H,52,53,54)
Plain Text
IUPAC Name
3-[(5-{[6-carboxy-4,5-dihydroxy-3-(sulfooxy)oxan-2-yl]oxy}-6-(hydroxymethyl)-3-(sulfoamino)-4-(sulfooxy)oxan-2-yl)oxy]-6-({5-acetamido-4,6-dihydroxy-2-[(sulfooxy)methyl]oxan-3-yl}oxy)-4-hydroxy-5-(sulfooxy)oxane-2-carboxylic acid
SMILES
CC(=O)NC1C(O)OC(COS(O)(=O)=O)C(OC2OC(C(OC3OC(CO)C(OC4OC(C(O)C(O)C4OS(O)(=O)=O)C(O)=O)C(OS(O)(=O)=O)C3NS(O)(=O)=O)C(O)C2OS(O)(=O)=O)C(O)=O)C1O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Carbohydrates
Substructures
  • Carbohydrates
  • Aminoglycosides
  • Glycerol and Derivatives
  • Hydroxy Compounds
  • Pyrans
  • Acetates
  • Acetals and Derivatives
  • Glucuronides
  • Amino Ketones
  • Sulfuric Acids and Derivatives
  • Sulfonyls
  • Ethers
  • Sulfate Esters
  • Carboxylic Acids and Derivatives
  • Alcohols and Polyols
  • Heterocyclic compounds
  • Carboxamides and Derivatives
Pharmacology
Indication For the prophylaxis of deep vein thrombosis, which may lead to pulmonary embolism, and also for the prophylaxis of ischemic complications of unstable angina and non-Q-wave myocardial infarction, when concurrently administered with aspirin.
Pharmacodynamics Enoxaparin is a highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from 3800 to 5000 daltons. Enoxaparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Enoxaparin is a well known and commonly used anticoagulant which has antithrombotic properties. Enoxaparin inhibits reactions that lead to the clotting of blood and the formation of fibrin clots both in vitro and in vivo. Enoxaparin acts at multiple sites in the normal coagulation system. Small amounts of enoxaparin in combination with antithrombin III (enoxaparin cofactor) can inhibit thrombosis by inactivating activated Factor X and inhibiting the conversion of prothrombin to thrombin. Once active thrombosis has developed, larger amounts of enoxaparin can inhibit further coagulation by inactivating thrombin and preventing the conversion of fibrinogen to fibrin. Enoxaparin also prevents the formation of a stable fibrin clot by inhibiting the activation of the fibrin stabilizing factor. Its use should be avoided in patients with a creatinine clearance less than 20mL/min. In these patients, unfractionated heparin should only be used. As for monitoring, active partial thromboplastin time (aPTT) will only increase at high doses of low molecular weight heparins (LMWH). Therefore, monitoring aPTT is not recommended. However, anti-Xa activity can be measured to monitor the efficacy of the LMWH.
Mechanism of action The mechanism of action of enoxaparin is antithrombin-dependent. It acts mainly by accelerating the rate of the neutralization of certain activated coagulation factors by antithrombin, but other mechanisms may also be involved. The antithrombotic effect of enoxaparin is well correlated to the inhibition of factor Xa. Enoxaparin interacts with Antithrombin III, Prothrombin and Factor X. Enoxaparin binds to and accelerates the activity of antithrombin III. By activating antithrombin III, enoxaparin preferentially potentiates the inhibition of coagulation factors Xa and IIa.
Absorption Mean absolute bioavailability of enoxaparin, after 1.5 mg/kg given subcutaneously, based on anti-Factor Xa activity is approximately 100% in healthy volunteers.
Volume of distribution
  • 4.3 L
Protein binding 80% bound-albumin
Metabolism

Undergoes desulfation and polymerization via the liver
Route of elimination Enoxaparin sodium is primarily metabolized in the liver by desulfation and/or depolymerization to lower molecular weight species with much reduced biological potency. Renal clearance of active fragments represents about 10% of the administered dose and total renal excretion of active and non-active fragments 40% of the dose.
Half life 4.5 hours
Clearance Not Available
Toxicity Mouse, median lethal dose greater than 5000 mg/kg. Another side effect is heparin induced thrombocytopenia (HIT syndrome). HIT is caused by an immunological reaction that makes platelets form clots within the blood vessels, thereby using up coagulation factors.
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00272 Enoxaparin Pathway SMP00272
Pharmacoeconomics
Manufacturers
  • Sandoz inc
  • Sanofi aventis us llc
Packagers
Dosage forms
Form Route Strength
Liquid Intravenous
Liquid Irrigation
Solution Intraperitoneal
Solution Intravenous
Solution Subcutaneous
Prices
Unit description Cost Unit
Lovenox 300 mg/3ml Solution 3ml Vial 281.47 USD vial
Lovenox 150 mg/ml Solution 1ml Syringe 140.94 USD syringe
Lovenox 100 mg/ml Solution 1ml Syringe 93.93 USD syringe
Lovenox 80 mg/0.8ml Solution 0.8ml Syringe 75.14 USD syringe
Lovenox 60 mg/0.6ml Solution 0.6ml Syringe 56.36 USD syringe
Lovenox 40 mg/0.4ml Solution 0.4ml Syringe 37.53 USD syringe
Lovenox Hp (0.8Ml/1Ml Syringe) 150 mg/ml Syringe 34.63 USD syringe
Lovenox 30 mg/0.3ml Solution 0.3ml Syringe 28.15 USD syringe
Lovenox (0.4 - 1 Ml Syringe) 100 mg/ml Syringe 23.09 USD syringe
Lovenox 100 mg/ml 23.09 USD syringe
Lovenox (0.3 Ml Syringe) 30 mg/syr Syringe 6.97 USD syringe
Patents
Country Patent Number Approved Expires
United States 5389618 1995-02-14 2012-02-14
Canada 2045433 2002-07-30 2011-06-25
Properties
State solid
Melting point Not Available
Experimental Properties
Property Value Source
water solubility > 200 mg/mL PhysProp
logP -13.2 PhysProp
Predicted Properties
Property Value Source
water solubility 1.08e+01 g/l ALOGPS
logP -1.68 ALOGPS
logP -8.35 ChemAxon Molconvert
logS -2.02 ALOGPS
pKa -2.37 ChemAxon Molconvert
hydrogen acceptor count 33 ChemAxon Molconvert
hydrogen donor count 15 ChemAxon Molconvert
polar surface area 610.49 ChemAxon Molconvert
rotatable bond count 20 ChemAxon Molconvert
refractivity 195.91 ChemAxon Molconvert
polarizability 93.37 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
PubChem Compound 772 Link_out
PubChem Substance 46507450 Link_out
ChemSpider 751 Link_out
Therapeutic Targets Database DAP000616 Link_out
PharmGKB PA449463 Link_out
Drug Product Database 2242692 Link_out
RxList http://www.rxlist.com/cgi/generic3/lovenox.htm Link_out
Drugs.com http://www.drugs.com/cdi/enoxaparin.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Enoxaparin Link_out
ATC Codes
  • B01AB05
  • B01AB01
AHFS Codes
  • 20:12.04.16
  • 92:00.00
PDB Entries Not Available
FDA label show (1.4 MB)
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions
  • Avoid danshen, dong quai, evening primrose oil, gingko, policosanol, willow bark
Targets

1. Antithrombin-III

Pharmacological action: yes
Actions: potentiator

Most important serine protease inhibitor in plasma that regulates the blood coagulation cascade. AT-III inhibits thrombin as well as factors IXa, Xa and XIa. Its inhibitory activity is greatly enhanced in the presence of heparin

Organism class: human
UniProt ID: P01008 Link_out
Gene: SERPINC1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Peng K, Wang C, Pang BS, Yang YH: [Effects of thrombolysis and anticoagulation on the functions of vascular endothelial cells and coagulation and fibrinolysis in patients with pulmonary thromboembolism] Zhonghua Jie He He Hu Xi Za Zhi. 2005 Sep;28(9):596-9. Pubmed
  2. Lee S, Gibson CM: Enoxaparin in acute coronary syndromes. Expert Rev Cardiovasc Ther. 2007 May;5(3):387-99. Pubmed
  3. Bisio A, Vecchietti D, Citterio L, Guerrini M, Raman R, Bertini S, Eisele G, Naggi A, Sasisekharan R, Torri G: Structural features of low-molecular-weight heparins affecting their affinity to antithrombin. Thromb Haemost. 2009 Nov;102(5):865-73. Pubmed

2. Coagulation factor X

Pharmacological action: yes
Actions: inhibitor

Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting

Organism class: human
UniProt ID: P00742 Link_out
Gene: F10 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Graff J, Picard-Willems B, Harder S: Monitoring effects of direct FXa-inhibitors with a new one-step prothrombinase-induced clotting time (PiCT) assay: comparative in vitro investigation with heparin, enoxaparin, fondaparinux and DX 9065a. Int J Clin Pharmacol Ther. 2007 Apr;45(4):237-43. Pubmed
  2. Berges A, Laporte S, Epinat M, Zufferey P, Alamartine E, Tranchand B, Decousus H, Mismetti P: Anti-factor Xa activity of enoxaparin administered at prophylactic dosage to patients over 75 years old. Br J Clin Pharmacol. 2007 Oct;64(4):428-38. Epub 2007 May 17. Pubmed
  3. Sanchez-Pena P, Hulot JS, Urien S, Ankri A, Collet JP, Choussat R, Lechat P, Montalescot G: Anti-factor Xa kinetics after intravenous enoxaparin in patients undergoing percutaneous coronary intervention: a population model analysis. Br J Clin Pharmacol. 2005 Oct;60(4):364-73. Pubmed
  4. Dalmora SL, Junior LB, Schmidt CA, Vaccari SF, Oliveira PR, Codevilla CF: Validation of the anti-factor Xa assay for the potency assessment of enoxaparin in pharmaceutical formulations. J AOAC Int. 2004 Nov-Dec;87(6):1305-8. Pubmed
  5. Paige JT, Gouda BP, Gaitor-Stampley V, Scalia PG, Klainer TE, Raum WJ, Martin LF: No correlation between anti-factor Xa levels, low-molecular-weight heparin, and bleeding after gastric bypass. Surg Obes Relat Dis. 2007 Jul-Aug;3(4):469-75. Epub 2007 Jun 12. Pubmed
Enzymes

1. Myeloperoxidase

Actions: Other

Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production of hypohalous acids, primarily hypochlorous acid in physiologic situations, and other toxic intermediates that greatly enhance PMN microbicidal activity

UniProt ID: P05164 Link_out
Gene: MPO Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Rudolph TK, Rudolph V, Witte A, Klinke A, Szoecs K, Lau D, Heitzer T, Meinertz T, Baldus S: Liberation of vessel adherent myeloperoxidase by enoxaparin improves endothelial function. Int J Cardiol. 2010 Apr 1;140(1):42-7. Epub 2008 Dec 2. Pubmed
Transporters
Searched, but no transporters found.
Carriers
Searched, but no carriers found.
Comments
Drug created on June 13, 2005 07:24 / Updated on October 11, 2011 14:15

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.