Thrombomodulin Alfa
Identification
- Generic Name
- Thrombomodulin Alfa
- DrugBank Accession Number
- DB05777
- Background
Thrombomodulin Alfa is a novel, recombinant and soluble thrombomodulin (ART-123). It is a human protein with both thrombin inhibiting and protein C stimulating activities, for the potential treatment of thromboembolism and blood clotting disorders, such as disseminated intravascular thromboembolism. 5
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Thrombolytic agents - Protein Chemical Formula
- Not Available
- Protein Average Weight
- Not Available
- Sequences
- Not Available
- Synonyms
- Thrombomodulin (human 498-amino acid fragment)
- Thrombomodulin Alfa
- External IDs
- ART-123
Pharmacology
- Indication
Investigated for use/treatment in blood preservative, blood (blood forming organ disorders, unspecified), sepsis and septicemia, and thrombosis.
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Contraindications & Blackbox WarningsWith our commercial data, access important information on dangerous risks, contraindications, and adverse effects.Our Blackbox Warnings cover Risks, Contraindications, and Adverse Effects- Pharmacodynamics
Thrombomodulin (TM) alfa, a recombinant human soluble TM, enhances activation of pro-carboxypeptidase B2 (pro-CPB2) by thrombin. Activated pro-CPB2 (CPB2) exerts anti-inflammatory and anti-fibrinolytic activities.
- Mechanism of action
Thrombomodulin alfa is a soluble form of recombinant human thrombomodulin comprising all extracellular domains of thrombomodulin. Bound to thrombin, Thrombomodulin alfa inhibits its procoagulant activity and promotes activation of protein C. Thrombomodulin alfa inhibits thrombin generation by the activation of protein C and the subsequent inactivation of factor Va in the presence of protein S. Thrombomodulin alfa attenuates the extension of the clot by inhibiting further thrombin generation on clots, while other anticoagulants inhibit the initiation of clot formation. A higher concentration of Thrombomodulin alfa is needed to affect clotting time and platelet aggregation than thrombin generation.
Target Actions Organism AProthrombin inhibitorHumans UCoagulation factor V Not Available Humans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
rapidly eliminated through liver
- Half-life
2–3 days after sc injection; 19.82 +/- 2.10 hours after IV injection
- Clearance
7-10 days
- Adverse Effects
Reduce medical errorsand improve treatment outcomes with our comprehensive & structured data on drug adverse effects.Reduce medical errors & improve treatment outcomes with our adverse effects data- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- Not Available
Products
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- Recomodulin
Categories
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Carbohydrates
- Glycoconjugates
- Glycoproteins
- Membrane Glycoproteins
- Membrane Proteins
- Platelet Membrane Glycoproteins
- Proteins
- Receptors, Cell Surface
- Receptors, G-Protein-Coupled
- Receptors, Immunologic
- Receptors, Peptide
- Receptors, Proteinase-Activated
- Receptors, Thrombin
- Chemical TaxonomyProvided by Classyfire
- Description
- Not Available
- Kingdom
- Organic Compounds
- Super Class
- Organic Acids
- Class
- Carboxylic Acids and Derivatives
- Sub Class
- Amino Acids, Peptides, and Analogues
- Direct Parent
- Peptides
- Alternative Parents
- Not Available
- Substituents
- Not Available
- Molecular Framework
- Not Available
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 2VU8WT49WX
- CAS number
- 120313-91-9
References
- General References
- Matsusaki M, Omichi M, Maruyama I, Akashi M: Physical adsorption of human thrombomodulin (ART-123) onto polymeric biomaterials for developing an antithrombogenic blood-contacting material. J Biomed Mater Res A. 2008 Jan;84(1):1-9. [Article]
- Saito H, Maruyama I, Shimazaki S, Yamamoto Y, Aikawa N, Ohno R, Hirayama A, Matsuda T, Asakura H, Nakashima M, Aoki N: Efficacy and safety of recombinant human soluble thrombomodulin (ART-123) in disseminated intravascular coagulation: results of a phase III, randomized, double-blind clinical trial. J Thromb Haemost. 2007 Jan;5(1):31-41. Epub 2006 Oct 13. [Article]
- Kearon C, Comp P, Douketis J, Royds R, Yamada K, Gent M: Dose-response study of recombinant human soluble thrombomodulin (ART-123) in the prevention of venous thromboembolism after total hip replacement. J Thromb Haemost. 2005 May;3(5):962-8. [Article]
- Moll S, Lindley C, Pescatore S, Morrison D, Tsuruta K, Mohri M, Serada M, Sata M, Shimizu H, Yamada K, White GC 2nd: Phase I study of a novel recombinant human soluble thrombomodulin, ART-123. J Thromb Haemost. 2004 Oct;2(10):1745-51. [Article]
- Khorchidi S, Bantleon R, Kehlbach R, Tepe G, Wiskirchen J, Duda SH: ART-123 Asahi Kasei. Curr Opin Investig Drugs. 2002 Aug;3(8):1196-8. [Article]
- Tawara S, Sakai T, Matsuzaki O: Anti-inflammatory and anti-fibrinolytic effects of thrombomodulin alfa through carboxypeptidase B2 in the presence of thrombin. Thromb Res. 2016 Nov;147:72-79. doi: 10.1016/j.thromres.2016.09.011. Epub 2016 Sep 17. [Article]
- TOXNET [Link]
- Bloodjournal [Link]
- External Links
- PubChem Substance
- 347910227
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Treatment Disseminated Intravascular Coagulation (DIC) 1 3 Completed Treatment Coagulation Disorders / Severe Sepsis 1 3 Completed Treatment Idiopathic Pulmonary Fibrosis (IPF) 1 3 Withdrawn Treatment Sepsis and Coagulopathy 1 2 Completed Prevention Postoperative Stage II/III Colon Cancer 1 2 Completed Treatment Disseminated Intravascular Coagulation (DIC) / Sepsis 1 2 Not Yet Recruiting Prevention Chemotherapy Induced Peripheral Neuropathy (CIPN) / Chemotherapy-induced Peripheral Neuropathy (CIPN) 1 2 Withdrawn Treatment Disseminated Intravascular Coagulation (DIC) / Sepsis 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Thrombospondin receptor activity
- Specific Function
- Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostas...
- Gene Name
- F2
- Uniprot ID
- P00734
- Uniprot Name
- Prothrombin
- Molecular Weight
- 70036.295 Da
References
- Thompson EA, Salem HH: Inhibition by human thrombomodulin of factor Xa-mediated cleavage of prothrombin. J Clin Invest. 1986 Jul;78(1):13-7. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Copper ion binding
- Specific Function
- Central regulator of hemostasis. It serves as a critical cofactor for the prothrombinase activity of factor Xa that results in the activation of prothrombin to thrombin.
- Gene Name
- F5
- Uniprot ID
- P12259
- Uniprot Name
- Coagulation factor V
- Molecular Weight
- 251701.245 Da
Drug created on November 18, 2007 18:27 / Updated on February 21, 2021 18:51