DT-Web

DB00001 - Lepirudin


Identification
Name Lepirudin
Accession Number DB00001 (BIOD00024, BTD00024)
Type biotech
Description Lepirudin is identical to natural hirudin except for substitution of leucine for isoleucine at the N-terminal end of the molecule and the absence of a sulfate group on the tyrosine at position 63. It is produced via yeast cells.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 6963.4250
Groups approved
Monoisotopic Weight Not Available
Pharmacology
Indication For the treatment of heparin-induced thrombocytopenia
Mechanism of action Lepirudin forms a stable non-covalent complex with alpha-thrombin, thereby abolishing its ability to cleave fibrinogen and initiate the clotting cascade. The inhibition of thrombin prevents the blood clotting cascade.
Absorption Bioavailability is 100% following injection.
Protein binding Not Available
Biotransformation Lepirudin is thought to be metabolized by release of amino acids via catabolic hydrolysis of the parent drug. However, con-clusive data are not available. About 48% of the administration dose is excreted in the urine which consists of unchanged drug (35%) and other fragments of the parent drug.
Route of elimination Lepirudin is thought to be metabolized by release of amino acids via catabolic hydrolysis of the parent drug. About 48% of the administration dose is excreted in the urine which consists of unchanged drug (35%) and other fragments of the parent drug.
Toxicity In case of overdose (eg, suggested by excessively high aPTT values) the risk of bleeding is increased.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Ginkgo biloba Additive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.
Treprostinil The prostacyclin analogue, Treprostinil, increases the risk of bleeding when combined with the anticoagulant, Lepirudin. Monitor for increased bleeding during concomitant thearpy.
Food Interactions Not Available

Targets


Prothrombin
Name Prothrombin
Gene Name F2
Pharmacological action yes
Actions inhibitor
References
  • Turpie AG: Anticoagulants in acute coronary syndromes. Am J Cardiol. 1999 Sep 2;84(5A):2M-6M. - Pubmed
  • Warkentin TE: Venous thromboembolism in heparin-induced thrombocytopenia. Curr Opin Pulm Med. 2000 Jul;6(4):343-51. - Pubmed
  • Eriksson BI: New therapeutic options in deep vein thrombosis prophylaxis. Semin Hematol. 2000 Jul;37(3 Suppl 5):7-9. - Pubmed
  • Fabrizio MC: Use of ecarin clotting time (ECT) with lepirudin therapy in heparin-induced thrombocytopenia and cardiopulmonary bypass. J Extra Corpor Technol. 2001 May;33(2):117-25. - Pubmed
  • Szaba FM, Smiley ST: Roles for thrombin and fibrin(ogen) in cytokine/chemokine production and macrophage adhesion in vivo. Blood. 2002 Feb 1;99(3):1053-9. - Pubmed
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 1.5668

Predictions


Id Partner name Gene Name Score
3176 Trypsin-1 PRSS1 0.1044
239 Coagulation factor X F10 0.0394
1074 Urokinase-type plasminogen activator PLAU 0.0362
369 Coagulation factor VII F7 0.0173
3119 Fimbrial protein pilE1 0.0168
6564 Prephenate dehydrogenase tyrA 0.0122
6240 Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 PIN1 0.0122
2331 HTH-type transcriptional regulator qacR qacR 0.01
6461 HTH-type transcriptional regulator qacR qacR 0.01
6828 TetR family transcriptional repressor LfrR lfrR 0.0095
256 Tyrosyl-tRNA synthetase, cytoplasmic YARS 0.0093
3384 Macrophage migration inhibitory factor MIF 0.009
19 Coagulation factor VIII F8 0.0083
1757 Myeloperoxidase MPO 0.0083
798 Osteocalcin BGLAP 0.008
3831 Low-density lipoprotein receptor-related protein 1 LRP1 0.0075
3851 Serine protease hepsin HPN 0.0071
448 Vitamin K-dependent gamma-carboxylase GGCX 0.0064
243 Ribosyldihydronicotinamide dehydrogenase [quinone] NQO2 0.0049
4757 Cytochrome P450 2C9 CYP2C9 0.0048
4165 P2Y purinoceptor 2 P2RY2 0.0047
400 Coagulation factor IX F9 0.0039
5461 Coagulation factor IX F9 0.0039
1547 Coagulation factor XI F11 0.0039
2654 Complement control protein C3L 0.0037
1959 Platelet factor 4 PF4 0.0035
3865 Serpin B6 SERPINB6 0.0035
1986 Ceruloplasmin CP 0.0035
1245 Vitamin K-dependent protein S PROS1 0.0035
4118 Cytochrome P450 3A5 CYP3A5 0.0035
430 Follicle-stimulating hormone receptor FSHR 0.0034
5766 NAD-dependent deacetylase sirtuin-5 SIRT5 0.0034
422 Vitamin K-dependent protein C PROC 0.0033
3842 Multiple coagulation factor deficiency protein 2 MCFD2 0.0033
3841 ERGIC-53 protein LMAN1 0.0033
3840 Asialoglycoprotein receptor 2 ASGR2 0.0033
1847 78 kDa glucose-regulated protein HSPA5 0.0033
1635 von Willebrand factor VWF 0.0033
5455 Arylsulfatase A ARSA 0.0032
3833 Plasma serine protease inhibitor SERPINA5 0.0031
4604 Liver carboxylesterase 1 CES1 0.0031
2072 Endothelial protein C receptor PROCR 0.0031
46 Coagulation factor V F5 0.0031
814 Ryanodine receptor 1 RYR1 0.0029
4512 Cytochrome P450 3A4 CYP3A4 0.0028
1516 Calnexin CANX 0.0028
6018 UDP-glucuronosyltransferase 1-9 UGT1A9 0.0027
2981 Phospholipase A2, membrane associated PLA2G2A 0.0026
2021 Thrombomodulin THBD 0.0026
6178 UDP-glucuronosyltransferase 2B7 UGT2B7 0.0025
3830 Calreticulin CALR 0.0023
3839 Phytanoyl-CoA dioxygenase, peroxisomal PHYH 0.0023
267 Plasminogen activator inhibitor 1 SERPINE1 0.0023
723 Cytosolic phospholipase A2 PLA2G4A 0.0023
1588 Multidrug resistance protein 1 ABCB1 0.0016
604 Vitamin K-dependent protein Z PROZ 0.0014
4081 Vitamin K epoxide reductase complex subunit 1-like protein 1 VKORC1L1 0.0014
2157 NAD(P)H dehydrogenase [quinone] 1 NQO1 0.001
787 Vitamin K epoxide reductase complex subunit 1 VKORC1 0.001
3917 Methylenetetrahydrofolate reductase MTHFR 0.0009
6020 Aldehyde oxidase AOX1 0.0009
3947 Xanthine dehydrogenase/oxidase XDH 0.0008
5718 Cytochrome P450 2A6 CYP2A6 0.0006
6024 Cytochrome P450 1A1 CYP1A1 0.0006
6013 Cytochrome P450 2E1 CYP2E1 0.0006
4200 Cytochrome P450 1A2 CYP1A2 0.0005
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