Identification

Name
Thrombomodulin Alfa
Accession Number
DB05777
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Thrombolytic agents
Description

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]

Protein chemical formula
Not Available
Protein average weight
Not Available
Sequences
Not Available
Synonyms
  • Thrombomodulin (human 498-amino acid fragment)
External IDs
ART-123
International/Other Brands
Recomodulin
Categories
UNII
2VU8WT49WX
CAS number
120313-91-9

Pharmacology

Indication

Investigated for use/treatment in blood preservative, blood (blood forming organ disorders, unspecified), sepsis and septicemia, and thrombosis.

Structured Indications
Not Available
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.

TargetActionsOrganism
AProthrombin
inhibitor
Human
UCoagulation factor VNot AvailableHuman
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

Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. 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. [PubMed:17584906]
  2. 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. [PubMed:17059423]
  3. 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. [PubMed:15869592]
  4. 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. [PubMed:15456485]
  5. 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. [PubMed:12211414]
  6. 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. [PubMed:27693845]
  7. TOXNET [Link]
  8. Bloodjournal [Link]
External Links
PubChem Substance
347910227

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2Active Not RecruitingPreventionPostoperative Stage II/III Colon Cancer1
2CompletedTreatmentDisseminated Intravascular Coagulation (DIC) / Sepsis1
2WithdrawnTreatmentDisseminated Intravascular Coagulation (DIC) / Sepsis1
3RecruitingTreatmentCoagulation Disorders / Severe Sepsis1
3RecruitingTreatmentIdiopathic Pulmonary Fibrosis (IPF)1
4CompletedTreatmentDisseminated Intravascular Coagulation (DIC)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

Taxonomy

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

Targets

Kind
Protein
Organism
Human
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
  1. Thompson EA, Salem HH: Inhibition by human thrombomodulin of factor Xa-mediated cleavage of prothrombin. J Clin Invest. 1986 Jul;78(1):13-7. [PubMed:3013935]
Kind
Protein
Organism
Human
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 11:27 / Updated on November 06, 2017 06:45