DT-Web

DB00569 - Fondaparinux sodium


Identification
Name Fondaparinux sodium
Accession Number DB00569 (APRD00500)
Type small molecule
Description Fondaparinux (Arixtra) is a synthetic pentasaccharide anticoagulant. Apart from the O-methyl group at the reducing end of the molecule, the identity and sequence of the five monomeric sugar units contained in fondaparinux is identical to a sequence of five monomeric sugar units that can be isolated after either chemical or enzymatic cleavage of the polymeric glycosaminoglycan heparin and heparan sulfate (HS). This monomeric sequence in heparin and HS is thought to form the high affinity binding site for the natural anti-coagulant factor, antithrombin III (ATIII). Binding of heparin/HS to ATIII has been shown to increase the anti-coagulant activity of antithrombin III 1000-fold. Fondaparinux potentiates the neutralizing action of ATIII on activated Factor X 300-fold. Fondaparinux may be used: to prevent venous thromboembolism in patients who have undergone orthopedic surgery of the lower limbs (e.g. hip fracture, hip replacement and knee surgery); to prevent VTE in patients undergoing abdominal surgery who are are at high risk of thromboembolic complications; in the treatment of deep vein thrombosis (DVT) and pumonary embolism (PE); in the management of unstable angina (UA) and non-ST segment elevation myocardial infarction (NSTEMI); and in the management of ST segment elevation myocardial infarction (STEMI).
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 1730.097
Groups approved
Monoisotopic Weight 1728.786427203
Pharmacology
Indication Approved for: (1) prophylaxis of VTE for up to one month post surgery in patients undergoing orthopedic surgery of the lower limbs such as hip fracture, hip replacement and knee surgery; (2) prophylaxis of VTE patients undergoing abdominal surgery who are at high risk of thromboembolic complications (e.g. patients undergoing abdominal cancer surgery); (3) treatment of acute DVT and PE; (4) management of UA and NSTEMI for the prevention of death and subsequent myocardial infarction (MI); and (5) management of STEMI for the prevention of death and myocardial reinfarction in patients who are managed with thrombolytics or who are initially to receive no form of reperfusion therapy. Fondaparinux should not be used as the sole anticoagulant during percutaneous coronary intervention (PCI) due to an increased risk of guiding catheter thrombosis.
Mechanism of action The antithrombotic activity of fondaparinux is the result of ATIII-mediated selective inhibition of Factor Xa. By selectively binding to ATIII, Fondaparinux potentiates (about 300 times) the neutralization of Factor Xa by ATIII. Neutralization of Factor Xa interrupts the blood coagulation cascade and thus inhibits thrombin formation and thrombus development. It is thought that fondaparinux is unlikely to induce thrombocytopenia via a heparin-induced thrombocytopenia (HIT)-like mechanism given its chemical structure (PMID 19825921). As a result, fondaparinux has been used as an alternative anticoagulant in heparin-induced thrombocytopenia (HIT) patients (PMID 19737996, 19432027, 18217156). However, it is important to note that rare cases of HIT have been reported in patients treated with fondaparinux (PMID 20351685, 20351686).
Absorption 100% bioavailability when administered subcutaneously
Protein binding 94% in vitro protein binding specifically to ATIII
Biotransformation Not metabolized
Route of elimination In individuals with normal kidney function, fondaparinux is eliminated in urine mainly as unchanged drug.
Toxicity As with other anticoagulants, the main concern is increased bleed risk. The risk of hemorrhage may increase with decreased renal function, body mass less than 50 kg, and moderate to severe hepatic function.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Drotrecogin alfa Drotrecogin alfa may increase the adverse effects of fondaparinux, resulting in excessive bleeding. Concomitant use should be avoided.
Ginkgo biloba Additive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.
Food Interactions Not Available

Targets


Antithrombin-III
Name Antithrombin-III
Gene Name SERPINC1
Pharmacological action yes
Actions potentiator
References
  • Paolucci F, Clavies MC, Donat F, Necciari J: Fondaparinux sodium mechanism of action: identification of specific binding to purified and human plasma-derived proteins. Clin Pharmacokinet. 2002;41 Suppl 2:11-8. - Pubmed
  • Cheng JW: Fondaparinux: a new antithrombotic agent. Clin Ther. 2002 Nov;24(11):1757-69; discussion 1719. - Pubmed
  • Dager WE, Andersen J, Nutescu E: Special considerations with fondaparinux therapy: heparin-induced thrombocytopenia and wound healing. Pharmacotherapy. 2004 Jul;24(7 Pt 2):88S-94S. - Pubmed
  • Donat F, Duret JP, Santoni A, Cariou R, Necciari J, Magnani H, de Greef R: The pharmacokinetics of fondaparinux sodium in healthy volunteers. Clin Pharmacokinet. 2002;41 Suppl 2:1-9. - Pubmed
DTHybrid score 0.6281
Coagulation factor X
Name Coagulation factor X
Gene Name F10
Pharmacological action yes
Actions inhibitor
References
  • Grouzi E, Kyriakou E, Panagou I, Spiliotopoulou I: Fondaparinux for the treatment of acute heparin-induced thrombocytopenia: a single-center experience. Clin Appl Thromb Hemost. 2010 Dec;16(6):663-7. Epub 2009 Oct 13. - Pubmed
DTHybrid score 1.5497

Predictions


Id Partner name Gene Name Score
852 Heparin cofactor 2 SERPIND1 0.2155
2058 P-selectin SELP 0.167
1719 Heparanase HPSE 0.1183
2020 Stromal cell-derived factor 1 CXCL12 0.0902
1953 Proto-oncogene protein c-fos FOS 0.09
647 Integrin alpha-4 ITGA4 0.0783
54 Prothrombin F2 0.0698
1334 Tissue factor pathway inhibitor TFPI 0.0602
1757 Myeloperoxidase MPO 0.0521
183 Vascular endothelial growth factor A VEGFA 0.0304
369 Coagulation factor VII F7 0.0188
448 Vitamin K-dependent gamma-carboxylase GGCX 0.0177
798 Osteocalcin BGLAP 0.0167
3831 Low-density lipoprotein receptor-related protein 1 LRP1 0.016
6182 Cytochrome P450 2J2 CYP2J2 0.0145
19 Coagulation factor VIII F8 0.0113
2139 Tissue factor F3 0.0111
3851 Serine protease hepsin HPN 0.01
400 Coagulation factor IX F9 0.0084
5461 Coagulation factor IX F9 0.0084
1547 Coagulation factor XI F11 0.0081
422 Vitamin K-dependent protein C PROC 0.0071
3842 Multiple coagulation factor deficiency protein 2 MCFD2 0.007
3841 ERGIC-53 protein LMAN1 0.007
3840 Asialoglycoprotein receptor 2 ASGR2 0.007
1847 78 kDa glucose-regulated protein HSPA5 0.007
1635 von Willebrand factor VWF 0.007
4118 Cytochrome P450 3A5 CYP3A5 0.0067
1588 Multidrug resistance protein 1 ABCB1 0.0063
1516 Calnexin CANX 0.0061
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
4512 Cytochrome P450 3A4 CYP3A4 0.0055
3175 Glutamate--cysteine ligase gshA 0.0053
3830 Calreticulin CALR 0.005
3839 Phytanoyl-CoA dioxygenase, peroxisomal PHYH 0.0049
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
4200 Cytochrome P450 1A2 CYP1A2 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
604 Vitamin K-dependent protein Z PROZ 0.003
4081 Vitamin K epoxide reductase complex subunit 1-like protein 1 VKORC1L1 0.003
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
1245 Vitamin K-dependent protein S PROS1 0.0028
4666 Fucose-binding lectin PA-IIL lecB 0.0028
595 Fibrinogen alpha chain FGA 0.0028
2372 Bifunctional tail protein 9 0.0028
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0027
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
243 Ribosyldihydronicotinamide dehydrogenase [quinone] NQO2 0.0024
2430 Chondroitinase B cslB 0.0023
3814 Complement C1r subcomponent C1R 0.0023
2581 Chondroitinase AC cslA 0.0022
4924 Cytochrome P450 2C8 CYP2C8 0.0022
6847 Lactase-phlorizin hydrolase LCT 0.0022
6307 Ig gamma-2 chain C region IGHG2 0.0022
2157 NAD(P)H dehydrogenase [quinone] 1 NQO1 0.0021
6016 Cytochrome P450 2C19 CYP2C19 0.0021
6500 Phospholipase A2 PLA2G1B 0.0021
787 Vitamin K epoxide reductase complex subunit 1 VKORC1 0.0021
2207 Rhodopsin RHO 0.0021
4757 Cytochrome P450 2C9 CYP2C9 0.002
3917 Methylenetetrahydrofolate reductase MTHFR 0.0019
4785 Ig gamma-1 chain C region IGHG1 0.0018
6020 Aldehyde oxidase AOX1 0.0018
76 Nitric-oxide synthase, brain NOS1 0.0018
4604 Liver carboxylesterase 1 CES1 0.0018
3947 Xanthine dehydrogenase/oxidase XDH 0.0017
952 Dipeptidyl peptidase 4 DPP4 0.0016
3923 Cholinesterase BCHE 0.0014
5718 Cytochrome P450 2A6 CYP2A6 0.0013
20 Prostaglandin G/H synthase 1 PTGS1 0.0013
6024 Cytochrome P450 1A1 CYP1A1 0.0013
6013 Cytochrome P450 2E1 CYP2E1 0.0012
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