DT-Web

DB06822 - Tinzaparin


Identification
Name Tinzaparin
Accession Number DB06822
Type small molecule
Description Tinzaparin is a low molecular weight heparin (LMWH), produced by enzymatic depolymerization of unfractionated heparin from porcine intestinal mucosa. It is a heterogeneous mixture of with an average molecular weight between 5500 and 7500 daltons. Tinzaparin is composed of molecules with and without a special site for high affinity binding to antithrombin III (ATIII). This complex greatly accelerates the inhibition of factor Xa. It is an anticoagulant and considered an antithrombotic. Tinzaparin must be given either subcutaneously or parenterally. LMWHs are less effective at inactivating factor IIa due to their shorter length compared to unfractionated heparin.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight Not Available
Groups approved
Monoisotopic Weight Not Available
Pharmacology
Indication Tinzaparin is used for the prevention of postoperative venous thromboembolism in patients undergoing orthopedic surgery and in patients undergoing general surgery who are at high risk of developing postoperative venous thromboembolism. It is also used for the treatment of deep vein thrombosis and/or pulmonary embolism. It is indicated for use in preventing clot formation in indwelling intravenous lines for hemodialysis.
Mechanism of action Tinzaparin binds to the plasma protein antithrombin III, forming a complex with then accelerates the inhibition of factor Xa. Its affinity for factor Xa is 2-4 times greater than that of unbound ATIII. The inactivation of factor Xa in turn will exponentially generation of thrombin (factor IIa) molecules, which is needed to activate fibrinogen to fibrin. The coagulation cascade is inhibited because fibrin cannot be formed in the presence of tinzaparin. Like all LMWH, it cannot be given intramuscularly due to increased risk of hematoma.
Absorption Subcutaneous injection - about 90% when measured as anti-Xa activity versus 67% for anti-IIa activity.
Protein binding Low protein binding compared to unfractionated heparin.
Biotransformation Sulfation and polymerization occurs in the liver.
Route of elimination Linear elimination through kidneys
Toxicity Osteoporosis with increasing duration of use, bleeding, alopecia, heparin induced thrombocytopenia (HIT). All of these adverse drug reactions occur less with LMWH compared to unfractionated heparin. Tinzaparin showed no toxic effects at doses up to 5 mg/kg in mice, rats, or dogs in standard acute, subacute, and chronic toxicity studies.
Affected organisms Not Available
Interactions
Drug Interactions
Drug Mechanism of interaction
Drotrecogin alfa Low molecular weight heparins (LMWHs) such as tinzaparin may enhance the adverse/toxic effects of drotrecogin alfa. Bleeding may occur. The potential benefits of drotrecogin alfa should be weighed against the increased risk of bleeding in patients on therapeutic doses of LMWHs.
Food Interactions
  • Herbs with anticoagulant/antiplatelet properties (ginger, gingko, garlic) may increase the risk of bleeding.

Targets


Antithrombin-III
Name Antithrombin-III
Gene Name SERPINC1
Pharmacological action yes
Actions potentiator
References
  • 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
  • Florian-Kujawski M, Hoppensteadt D, Maddineni J, Ziegler H, Fareed J: Differential regulation of thrombin activatable fibrinolytic inhibitor by low molecular weight heparins. Pharmacologic implications. Int Angiol. 2004 Dec;23(4):346-54. - Pubmed
  • Morris TA, Jacobson A, Marsh JJ, Lane JR: Pharmacokinetics of UH and LMWH are similar with respect to antithrombin activity. Thromb Res. 2005;115(1-2):45-51. - Pubmed
DTHybrid score 1.1394
Integrin alpha-4
Name Integrin alpha-4
Gene Name ITGA4
Pharmacological action unknown
Actions inhibitor
References
  • Schlesinger M, Simonis D, Schmitz P, Fritzsche J, Bendas G: Binding between heparin and the integrin VLA-4. Thromb Haemost. 2009 Nov;102(5):816-22. - Pubmed
DTHybrid score 0.9894
Stromal cell-derived factor 1
Name Stromal cell-derived factor 1
Gene Name CXCL12
Pharmacological action unknown
Actions binder
References
  • Koo CY, Sen YP, Bay BH, Yip GW: Targeting heparan sulfate proteoglycans in breast cancer treatment. Recent Pat Anticancer Drug Discov. 2008 Nov;3(3):151-8. - Pubmed
DTHybrid score 1.0831

Enzymes


A disintegrin and metalloproteinase with thrombospondin motifs 4
Name A disintegrin and metalloproteinase with thrombospondin motifs 4
Gene Name Not Available
Actions inhibitor
References
  • Mousa SA: Effect of low molecular weight heparin and different heparin molecular weight fractions on the activity of the matrix-degrading enzyme aggrecanase: structure-function relationship. J Cell Biochem. 2005 May 1;95(1):95-8. - Pubmed
DTHybrid score Not Available

Predictions


Id Partner name Gene Name Score
852 Heparin cofactor 2 SERPIND1 0.2155
2058 P-selectin SELP 0.1514
239 Coagulation factor X F10 0.1206
1719 Heparanase HPSE 0.1019
1953 Proto-oncogene protein c-fos FOS 0.09
1783 Intercellular adhesion molecule 1 ICAM1 0.0709
3814 Complement C1r subcomponent C1R 0.0475
1334 Tissue factor pathway inhibitor TFPI 0.047
3816 Complement C1q subcomponent subunit B C1QB 0.0457
3815 Complement C1q subcomponent subunit A C1QA 0.0457
3817 Complement C1q subcomponent subunit C C1QC 0.0457
1102 Low affinity immunoglobulin gamma Fc region receptor III-B FCGR3B 0.0452
3818 Low affinity immunoglobulin gamma Fc region receptor III-A FCGR3A 0.0452
3819 Low affinity immunoglobulin gamma Fc region receptor II-a FCGR2A 0.0452
3821 Low affinity immunoglobulin gamma Fc region receptor II-c FCGR2C 0.0452
3820 Low affinity immunoglobulin gamma Fc region receptor II-b FCGR2B 0.0447
784 High affinity immunoglobulin gamma Fc receptor I FCGR1A 0.0443
1757 Myeloperoxidase MPO 0.0403
183 Vascular endothelial growth factor A VEGFA 0.0304
6589 Delta-hemolysin hld 0.0056
6424 Light-harvesting protein B-800/820 beta chain Not Available 0.0056
6591 ATP synthase C chain atpH 0.0056
6587 Rubredoxin rub 0.0056
6423 Light-harvesting protein B-800/820 alpha chain Not Available 0.0056
6586 Protein S100-G S100G 0.0056
6588 Methionyl-tRNA formyltransferase fmt 0.0056
4718 Putative ATP-dependent Clp protease proteolytic subunit, mitochondrial CLPP 0.0056
6592 Probable L-ascorbate-6-phosphate lactonase ulaG ulaG 0.0056
6585 HLA class I histocompatibility antigen, B-27 alpha chain HLA-B 0.0056
6593 Immunoglobulin G-binding protein G spg 0.0056
3175 Glutamate--cysteine ligase gshA 0.0053
6495 Cytochrome c oxidase subunit 7C, mitochondrial COX7C 0.0049
6493 Cytochrome c oxidase subunit 6C COX6C 0.0048
6498 Cytochrome c oxidase subunit 6B1 COX6B1 0.0048
6279 Beta-2-microglobulin B2M 0.0048
6497 Cytochrome c oxidase subunit 6A2, mitochondrial COX6A2 0.0048
6496 Cytochrome c oxidase subunit 8A, mitochondrial COX8A 0.0048
6499 Cytochrome c oxidase polypeptide 7A1, mitochondrial COX7A1 0.0048
6494 Cytochrome c oxidase subunit 7B, mitochondrial COX7B 0.0048
5793 Cytochrome c oxidase subunit 2 MT-CO2 0.0048
6559 Cytochrome c oxidase subunit 2 ctaC 0.0048
6669 Cytochrome c oxidase subunit 2 ctaC 0.0048
6490 Cytochrome c oxidase subunit 3 MT-CO3 0.0048
6491 Cytochrome c oxidase subunit 5A, mitochondrial COX5A 0.0048
6489 Cytochrome c oxidase subunit 4 isoform 1, mitochondrial COX4I1 0.0048
371 Cytochrome c oxidase subunit 1 MT-CO1 0.0048
6558 Cytochrome c oxidase subunit 1 ctaD 0.0048
6319 Respiratory nitrate reductase 1 gamma chain narI 0.0048
6318 Respiratory nitrate reductase 1 beta chain narH 0.0048
6317 Respiratory nitrate reductase 1 alpha chain narG 0.0048
6428 Light-harvesting protein B-800/850 beta chain Not Available 0.0045
6427 Light-harvesting protein B-800/850 alpha chain Not Available 0.0045
6533 Light-harvesting protein B-800/850 alpha chain A1 0.0045
6576 Geranylgeranyl transferase type-2 subunit beta RABGGTB 0.0042
6575 Geranylgeranyl transferase type-2 subunit alpha RABGGTA 0.0042
2132 Protein S100-B S100B 0.0041
4878 Glycoprotein hormones alpha chain CGA 0.0041
4856 CD209 antigen CD209 0.0041
1052 Cytotoxic T-lymphocyte protein 4 CTLA4 0.0041
1072 Granzyme B GZMB 0.0041
4871 Endo-beta-N-acetylglucosaminidase F3 endOF3 0.0041
4850 Beta-2-glycoprotein 1 APOH 0.0041
4880 Membrane cofactor protein CD46 0.0041
4889 Ig epsilon chain C region IGHE 0.0041
4189 Alpha-galactosidase A GLA 0.0041
4869 Major capsid protein A430L 0.0041
4852 Reticulon-4 receptor RTN4R 0.0041
4877 Beta-mannanase man 0.0041
442 Envelope glycoprotein gp41 0.0041
4859 Envelope glycoprotein env 0.0041
4845 ADAM 33 ADAM33 0.0041
757 Fusion glycoprotein F0 F 0.0041
4875 Fusion glycoprotein F0 F 0.0041
1563 Platelet glycoprotein Ib alpha chain GP1BA 0.0041
1354 Beta-glucuronidase GUSB 0.0041
4882 Dipeptidyl aminopeptidase-like protein 6 DPP6 0.0041
4721 Beta-1,4-mannanase manA 0.0041
3352 Structural polyprotein Not Available 0.0041
3628 Structural polyprotein Not Available 0.0041
4892 Structural polyprotein Not Available 0.0041
6352 Reaction center protein H chain puhA 0.0036
6456 Reaction center protein H chain puhA 0.0036
6682 Reaction center protein H chain puhA 0.0036
6353 Reaction center protein L chain pufL 0.0036
6454 Reaction center protein L chain pufL 0.0036
6683 Reaction center protein L chain pufL 0.0036
6351 Photosynthetic reaction center cytochrome c subunit pufC 0.0036
6354 Reaction center protein M chain pufM 0.0036
6455 Reaction center protein M chain pufM 0.0036
6684 Reaction center protein M chain pufM 0.0036
793 T-cell surface antigen CD2 CD2 0.0036
119 Carcinoembryonic antigen-related cell adhesion molecule 1 CEACAM1 0.0036
4861 Interleukin-6 receptor alpha chain IL6R 0.0036
4193 Atrial natriuretic peptide clearance receptor NPR3 0.0036
3837 Cytokine receptor common beta chain CSF2RB 0.0036
559 NADH-ubiquinone oxidoreductase chain 1 MT-ND1 0.0035
1184 Interferon beta IFNB1 0.0033
4857 Zinc-alpha-2-glycoprotein AZGP1 0.0033
1379 Interleukin-12 subunit beta IL12B 0.0033
6858 Inactive carboxylesterase 4 CES1P1 0.0033
4890 Hemagglutinin HA 0.0033
6566 Hemagglutinin Not Available 0.0033
3027 Streptavidin Not Available 0.0032
554 Low-density lipoprotein receptor LDLR 0.0032
2998 Sialic acid-binding Ig-like lectin 7 SIGLEC7 0.0031
6120 Cation-independent mannose-6-phosphate receptor IGF2R 0.0031
2297 Genome polyprotein Not Available 0.0031
2322 Genome polyprotein Not Available 0.0031
2694 Genome polyprotein Not Available 0.0031
2719 Genome polyprotein Not Available 0.0031
2860 Genome polyprotein Not Available 0.0031
2928 Genome polyprotein Not Available 0.0031
3160 Genome polyprotein Not Available 0.0031
3260 Genome polyprotein Not Available 0.0031
4783 Genome polyprotein Not Available 0.0031
5726 Genome polyprotein Not Available 0.0031
5779 Genome polyprotein Not Available 0.0031
5867 Genome polyprotein Not Available 0.0031
6253 Genome polyprotein Not Available 0.0031
6301 Genome polyprotein Not Available 0.0031
6380 Genome polyprotein Not Available 0.0031
6381 Genome polyprotein Not Available 0.0031
6437 Genome polyprotein Not Available 0.0031
6520 Genome polyprotein Not Available 0.0031
6521 Genome polyprotein Not Available 0.0031
6652 Genome polyprotein Not Available 0.0031
6734 Genome polyprotein Not Available 0.0031
6735 Genome polyprotein Not Available 0.0031
6736 Genome polyprotein Not Available 0.0031
6737 Genome polyprotein Not Available 0.0031
6738 Genome polyprotein Not Available 0.0031
6739 Genome polyprotein Not Available 0.0031
6744 Genome polyprotein Not Available 0.0031
6748 Genome polyprotein Not Available 0.0031
6894 Genome polyprotein Not Available 0.0031
6898 Genome polyprotein Not Available 0.0031
18 High affinity immunoglobulin epsilon receptor subunit alpha FCER1A 0.0031
3444 Cyanovirin-N Not Available 0.003
3140 Hemagglutinin-neuraminidase HN 0.003
3609 Hemagglutinin-neuraminidase HN 0.003
3258 Mannosyl-oligosaccharide alpha-1,2-mannosidase MSDC 0.003
1859 Prostatic acid phosphatase ACPP 0.0029
4787 Envelope glycoprotein gp160 env 0.0029
4820 Envelope glycoprotein gp160 env 0.0029
5727 Envelope glycoprotein gp160 env 0.0029
5682 Ribonuclease pancreatic RNASE1 0.0029
4666 Fucose-binding lectin PA-IIL lecB 0.0028
595 Fibrinogen alpha chain FGA 0.0028
2372 Bifunctional tail protein 9 0.0028
2577 Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase MAN1B1 0.0026
3480 Mannan endo-1,4-beta-mannosidase manA 0.0026
958 Insulin-like growth factor 1 receptor IGF1R 0.0025
64 Neuraminidase NA 0.0025
641 Neuraminidase NA 0.0025
2676 Neuraminidase NA 0.0025
3026 Neuraminidase NA 0.0025
3519 Neuraminidase NA 0.0025
6007 Neuraminidase NA 0.0025
1243 Cathepsin D CTSD 0.0024
1439 Lactotransferrin LTF 0.0024
1782 Neutrophil gelatinase-associated lipocalin LCN2 0.0024
2430 Chondroitinase B cslB 0.0023
2581 Chondroitinase AC cslA 0.0022
6847 Lactase-phlorizin hydrolase LCT 0.0022
6307 Ig gamma-2 chain C region IGHG2 0.0022
6500 Phospholipase A2 PLA2G1B 0.0021
2207 Rhodopsin RHO 0.0021
4785 Ig gamma-1 chain C region IGHG1 0.0018
76 Nitric-oxide synthase, brain NOS1 0.0018
4604 Liver carboxylesterase 1 CES1 0.0018
952 Dipeptidyl peptidase 4 DPP4 0.0016
3923 Cholinesterase BCHE 0.0014
20 Prostaglandin G/H synthase 1 PTGS1 0.0013
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