Repositioning Candidate Details
| Candidate ID: | R0195 |
| Source ID: | DB00569 |
| Source Type: | approved; investigational |
| Compound Type: | small molecule |
| Compound Name: | Fondaparinux |
| Synonyms: | Natural heparin pentasaccharide |
| Molecular Formula: | C31H53N3O49S8 |
| SMILES: | CO[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](O[C@@H]2O[C@H]([C@@H](O[C@H]3O[C@H](COS(O)(=O)=O)[C@@H](O[C@@H]4O[C@@H]([C@@H](O[C@H]5O[C@H](COS(O)(=O)=O)[C@@H](O)[C@H](O)[C@H]5NS(O)(=O)=O)[C@H](O)[C@H]4O)C(O)=O)[C@H](OS(O)(=O)=O)[C@H]3NS(O)(=O)=O)[C@H](O)[C@H]2OS(O)(=O)=O)C(O)=O)[C@H](O)[C@H]1NS(O)(=O)=O |
| Structure: |
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| DrugBank Description: | Fondaparinux (Arixtra) is a synthetic anticoagulant agent consisting of five monomeric sugar units and a O-methyl group at the reducing end of the molecule. It is structurally similar to polymeric glycosaminoglycan heparin and heparan sulfate (HS) when they are cleaved into monomeric units. The monomeric sequence in heparin and HS is thought to form the high affinity binding site for the natural anti-coagulant factor, antithrombin III (ATIII). Once bound to heparin or HS, the anticoagulant activity of ATIII is potentiated by 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). |
| CAS Number: | 104993-28-4 |
| Molecular Weight: | 1508.263 |
| DrugBank 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. |
| DrugBank Pharmacology: | Fondaparinux binds specifically to the natural anticoagulant factor, ATIII. Binding to ATIII potentiates the neutralizing action of ATIII on Factor Xa 300-times. Neutralization of Factor Xa decreases the conversion of prothrombin to thrombin, which subsequently decreases the conversion of fibrinogen to fibrin (loose meshwork). The decrease in thrombin also decreases the activation of Factor XIII, which decreases the conversion of fibrin in its loose meshwork form to its stabilized meshwork form. Disruption of the coagulation cascade effectively decreases the formation of blood clots. Fondaparinux does not inactivate thrombin (activated Factor II). According to the manufacturer, fondaparinux has no known effect on platelet function. In studies comparing fondaparinux to enoxaparin, decreases in platelet levels were observed in similar numbers of patients from both groups (2-5%) . At the recommended dose, Fondaparinux does not affect fibrinolytic activity or bleeding time. There is no antidote for fondaparinux. Monitoring of the anticoagulant activity of fondaparinux is not generally required. The anti-factor Xa assay may be used to monitor therapy in special populations such as those with renal impairment or who are pregnant. Complete blood count (CBC) and kidney function should be monitored during treatment. |
| DrugBank MoA: | 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 . As a result, fondaparinux has been used as an alternative anticoagulant in heparin-induced thrombocytopenia (HIT) patients . However, it is important to note that rare cases of HIT have been reported in patients treated with fondaparinux . |
| Targets: | Antithrombin-III potentiator; Coagulation factor X inhibitor |
| Inclusion Criteria: | Indication associated |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs |
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| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I08 | 114 | Cardiovascular system disease | A disease of anatomical entity which occurs in the blood, heart, blood vessels or the lymphatic system that passes nutrients (such as amino acids and electrolytes), gases, hormones, blood cells or lymph to and from cells in the body to help fight diseases and help stabilize body temperature and pH to maintain homeostasis. http://en.wikipedia.org/wiki/Circulatory_system | disease of anatomical entity | Details |