DT-Web

DB06779 - Dalteparin


Identification
Name Dalteparin
Accession Number DB06779
Type small molecule
Description Dalteparin, a low molecular weight heparin (LMWH) prepared by nitrous acid degradation of unfractionated heparin of porcine intestinal mucosa origin, is an anticoagulant. It is composed of strongly acidic sulphated polysaccharide chains with an average molecular weight of 5000 and about 90% of the material within the range of 2000-9000. LMWHs have a more predictable response, a greater bioavailability, and a longer anti-Xa half life than unfractionated heparin. Dalteparin can also be safely used in most pregnant women. Low molecular weight heparins 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 Dalteparin is used as a prophylaxis for deep-vein thrombosis and pulmonary embolisms in patients undergoing general surgery (e.g., abdominal, gynecologic, urologic), and in patients with acute medical conditions (e.g. cancer, bed rest, heart failure, severe lung disease). It is also used in patients who have severely restricted mobility, which poses a risk for thromboembolic complications. Dalteparin is also used concomitantly with aspirin and/or other therapy (e.g., nitrates, ?-adrenergic blockers, clopidogrel, platelet glycoprotein [GP] IIb/IIIa-receptor inhibitors) to reduce the risk of acute cardiac ischemic events. The patients who undergo this treatment combination have unstable angina or non-ST-segment elevation/non-Q-wave myocardial infarction (i.e., non-ST-segment elevation acute coronary syndromes). It is also used in the prevention of clotting during hemodialysis and hemofiltration in connection with acute renal failure or chronic renal insufficiency.
Mechanism of action Dalteparin potentiates the activity of ATIII, inhibiting the formation of both factor Xa and thrombin. The main difference between dalteparin and unfractionated heparin (UH) is that dalteparin preferentially inactivates factor Xa. As a result, only a slight increase in clotting time [(i.e. activated partial thomboplastin time (APTT)] is observed relative to UH. For this same reason, APTT is not used to monitor the effects of dalteparin except as an indicator for overdosage.
Absorption Almost completely absorbed after subcutaneous (sc) doses, with a bioavialability of about 87%.
Protein binding Less than unfractionated heparin, which is more than 90%.
Biotransformation Liver and the reticulo-endothelial system are the sites of biotransformation. They are partially metabolized by desulphatation and depolymerization.
Route of elimination After 4 hours, about 20% is seen in urine. Most of the remainder is found in the liver, gastrointestinal tract and kidney. The kidneys are the major site of dalteparin excretion (approximately 70% based on animal studies).
Toxicity Overdosage: hemorrhagic complications. Adverse Drug Reaction: (common) osteopenia with extended use; mild, reversible non-immunological thrombocytopenia; transient elevation of liver transaminases; alopecia. (uncommon): severe immunologically-mediated heparin-induced thrombocytopenia; anaphylactic reactions; skin rash, skin necrosis; retroperitoneal hemorrhage; angioedema
Affected organisms Not Available
Interactions
Drug Interactions
Drug Mechanism of interaction
Drotrecogin alfa Low molecular weight heparin (LMWH) such as dalteparin may enhance the adverse/toxic effect of drotrecogin alfa. Bleeding may occur.
Food Interactions
  • Herbs (anticoagulant/antiplatelet properties such as ginseng, ginkgo, ginger, garlic)

Targets


Antithrombin-III
Name Antithrombin-III
Gene Name SERPINC1
Pharmacological action yes
Actions potentiator
References
  • Frydman A: Low-molecular-weight heparins: an overview of their pharmacodynamics, pharmacokinetics and metabolism in humans. Haemostasis. 1996;26 Suppl 2:24-38. - Pubmed
  • Rey E, Rivard GE: Prophylaxis and treatment of thromboembolic diseases during pregnancy with dalteparin. Int J Gynaecol Obstet. 2000 Oct;71(1):19-24. - Pubmed
DTHybrid score 1.2586
Vascular endothelial growth factor A
Name Vascular endothelial growth factor A
Gene Name VEGFA
Pharmacological action yes
Actions inhibitor
References
  • Norrby K, Nordenhem A: Dalteparin, a low-molecular-weight heparin, promotes angiogenesis mediated by heparin-binding VEGF-A in vivo. APMIS. 2010 Dec;118(12):949-57. doi: 10.1111/j.1600-0463.2010.02635.x. Epub 2010 Oct 12. - Pubmed
  • Marchetti M, Vignoli A, Russo L, Balducci D, Pagnoncelli M, Barbui T, Falanga A: Endothelial capillary tube formation and cell proliferation induced by tumor cells are affected by low molecular weight heparins and unfractionated heparin. Thromb Res. 2008;121(5):637-45. Epub 2007 Aug 10. - Pubmed
  • Takahashi H, Ebihara S, Okazaki T, Asada M, Sasaki H, Yamaya M: A comparison of the effects of unfractionated heparin, dalteparin and danaparoid on vascular endothelial growth factor-induced tumour angiogenesis and heparanase activity. Br J Pharmacol. 2005 Oct;146(3):333-43. - Pubmed
DTHybrid score 0.766
Tissue factor pathway inhibitor
Name Tissue factor pathway inhibitor
Gene Name TFPI
Pharmacological action yes
Actions inhibitor
References
  • Mousa SA: Low-molecular-weight heparins in thrombosis and cancer: emerging links. Cardiovasc Drug Rev. 2004 Summer;22(2):121-34. - Pubmed
  • Naumnik B, Rydzewska-Rosolowska A, Mysliwiec M: Different Effects of Enoxaparin, Nadroparin, and Dalteparin on Plasma TFPI During Hemodialysis: A Prospective Crossover Randomized Study. Clin Appl Thromb Hemost. 2010 Aug 3. - Pubmed
  • Bendz B, Andersen TO, Sandset PM: Dose-dependent release of endogenous tissue factor pathway inhibitor by different low molecular weight heparins. Blood Coagul Fibrinolysis. 2000 Jun;11(4):343-8. - Pubmed
DTHybrid score 0.7288
P-selectin
Name P-selectin
Gene Name SELP
Pharmacological action unknown
Actions inhibitor
References
  • Rey E, Rivard GE: Prophylaxis and treatment of thromboembolic diseases during pregnancy with dalteparin. Int J Gynaecol Obstet. 2000 Oct;71(1):19-24. - Pubmed
DTHybrid score 1.0635

Enzymes


Heparanase
Name Heparanase
Gene Name HPSE
Actions substrate
References
  • Takahashi H, Ebihara S, Okazaki T, Asada M, Sasaki H, Yamaya M: A comparison of the effects of unfractionated heparin, dalteparin and danaparoid on vascular endothelial growth factor-induced tumour angiogenesis and heparanase activity. Br J Pharmacol. 2005 Oct;146(3):333-43. - Pubmed
DTHybrid score 0.9735

Predictions


Id Partner name Gene Name Score
239 Coagulation factor X F10 0.3577
1953 Proto-oncogene protein c-fos FOS 0.2772
852 Heparin cofactor 2 SERPIND1 0.2155
5377 Placenta growth factor PGF 0.1355
2139 Tissue factor F3 0.1236
3851 Serine protease hepsin HPN 0.1181
448 Vitamin K-dependent gamma-carboxylase GGCX 0.1104
369 Coagulation factor VII F7 0.0992
2020 Stromal cell-derived factor 1 CXCL12 0.0902
647 Integrin alpha-4 ITGA4 0.0783
1757 Myeloperoxidase MPO 0.0403
4857 Zinc-alpha-2-glycoprotein AZGP1 0.0344
1756 E-selectin SELE 0.0342
5414 Fiber protein L5 0.034
5418 Fiber protein L5 0.034
2723 Cholera enterotoxin subunit B ctxB 0.0318
5416 Coat protein VP1 Not Available 0.0296
3629 Endo-N-acetylneuraminidase Not Available 0.0296
1130 Lithostathine 1 alpha REG1A 0.0295
3547 Enterotoxin type B entB 0.0275
2324 Botulinum neurotoxin type B botB 0.0272
230 ATP-binding cassette transporter sub-family C member 8 ABCC8 0.0257
587 Serum albumin ALB 0.0246
2570 Tetanus toxin tetX 0.0238
4411 DNA protection during starvation protein dps 0.0197
5423 UPF0010 protein HI1317 HI_1317 0.0197
3780 Lipoprotein nlpI precursor nlpI 0.0197
5424 Endonuclease VIII-like 1 NEIL1 0.0197
4604 Liver carboxylesterase 1 CES1 0.0187
5787 Angiopoietin-1 receptor TEK 0.0182
4757 Cytochrome P450 2C9 CYP2C9 0.0178
3164 Biotin synthase bioB 0.0173
3186 Soluble calcium-activated nucleotidase 1 CANT1 0.0172
5036 Small inducible cytokine A8 CCL8 0.017
4385 Cytochrome c' Not Available 0.017
4967 Cytochrome c' cycA 0.017
5038 Cytochrome c' Not Available 0.017
5223 Cytochrome c' cycP 0.017
5012 Ig lambda chain V-II region MGC Not Available 0.017
3814 Complement C1r subcomponent C1R 0.0159
3583 6-phosphogluconolactonase pgl 0.0159
6104 Dimethylaniline monooxygenase [N-oxide-forming] 1 FMO1 0.0157
3221 Cytochrome c4 cc4 0.0156
3259 Autolysin lytA 0.0151
5023 Glycoside hydrolase Not Available 0.0148
5024 Glycoside hydrolase Not Available 0.0148
4771 Dissimilatory copper-containing nitrite reductase nir 0.0148
5006 RNASE4 protein RNASE4 0.0148
6016 Cytochrome P450 2C19 CYP2C19 0.0146
113 S-adenosylmethionine decarboxylase proenzyme AMD1 0.0145
1654 Interleukin-1 beta IL1B 0.0145
844 Epidermal growth factor receptor EGFR 0.0145
4905 Cytochrome c2 Not Available 0.0143
4939 Cytochrome c2 cycA 0.0143
4964 Cytochrome c2 cycA 0.0143
4979 Cytochrome c2 cycA 0.0143
6673 Cytochrome c2 cycA 0.0143
3817 Complement C1q subcomponent subunit C C1QC 0.0138
3816 Complement C1q subcomponent subunit B C1QB 0.0138
3815 Complement C1q subcomponent subunit A C1QA 0.0138
6101 Dimethylaniline monooxygenase [N-oxide-forming] 3 FMO3 0.0137
494 Caspase-1 CASP1 0.0136
1102 Low affinity immunoglobulin gamma Fc region receptor III-B FCGR3B 0.0136
3818 Low affinity immunoglobulin gamma Fc region receptor III-A FCGR3A 0.0136
3819 Low affinity immunoglobulin gamma Fc region receptor II-a FCGR2A 0.0136
3821 Low affinity immunoglobulin gamma Fc region receptor II-c FCGR2C 0.0136
2149 Angiogenin ANG 0.0136
3820 Low affinity immunoglobulin gamma Fc region receptor II-b FCGR2B 0.0135
2430 Chondroitinase B cslB 0.0134
784 High affinity immunoglobulin gamma Fc receptor I FCGR1A 0.013
1507 Cytochrome c CYCS 0.0126
3030 Salivary alpha-amylase AMY1A 0.0123
1374 Natriuretic peptides B NPPB 0.0122
1827 Gap junction alpha-1 protein GJA1 0.0121
1908 Vascular cell adhesion protein 1 VCAM1 0.0121
22 30S ribosomal protein S4 rpsD 0.0117
6714 30S ribosomal protein S4 rpsD 0.0117
2077 Caspase-3 CASP3 0.0116
6374 Disintegrin and metalloproteinase domain-containing protein 28 ADAM28 0.0116
65 Matrix metalloproteinase-9 Not Available 0.0112
140 30S ribosomal protein S9 rpsI 0.011
6719 30S ribosomal protein S9 rpsI 0.011
6725 30S ribosomal protein S9 rpsI 0.011
1181 Alpha-1-acid glycoprotein 1 ORM1 0.0103
194 NADH dehydrogenase [ubiquinone] 1 subunit C2 NDUFC2 0.0103
275 Arachidonate 5-lipoxygenase ALOX5 0.0098
4513 Pancreatic alpha-amylase AMY2A 0.0098
862 Multidrug resistance-associated protein 1 ABCC1 0.0097
4512 Cytochrome P450 3A4 CYP3A4 0.0095
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0089
1024 Solute carrier family 22 member 11 SLC22A11 0.008
6143 Solute carrier family 22 member 7 SLC22A7 0.0079
6142 Solute carrier family 22 member 8 SLC22A8 0.007
101 Potassium voltage-gated channel subfamily H member 2 KCNH2 0.0064
3947 Xanthine dehydrogenase/oxidase XDH 0.0064
1729 Solute carrier family 22 member 6 SLC22A6 0.0064
20 Prostaglandin G/H synthase 1 PTGS1 0.0061
193 Beta-1 adrenergic receptor ADRB1 0.0057
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
766 Beta-2 adrenergic receptor ADRB2 0.0056
3175 Glutamate--cysteine ligase gshA 0.0053
556 Alpha-1A adrenergic receptor ADRA1A 0.005
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
6024 Cytochrome P450 1A1 CYP1A1 0.0048
6013 Cytochrome P450 2E1 CYP2E1 0.0045
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
4200 Cytochrome P450 1A2 CYP1A2 0.004
1588 Multidrug resistance protein 1 ABCB1 0.0038
4119 Cytochrome P450 2D6 CYP2D6 0.0038
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
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
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
952 Dipeptidyl peptidase 4 DPP4 0.0016
3923 Cholinesterase BCHE 0.0014
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