Identification
NameThrombomodulin Alfa
Accession NumberDB05777
TypeBiotech
GroupsApproved, Investigational
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 structureNo structure small
Related Articles
Protein chemical formulaNot Available
Protein average weightNot Available
SequencesNot Available
Synonyms
Thrombomodulin (human 498-amino acid fragment)
External IDs ART-123
Product Ingredients Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
RecomodulinNot Available
Brand mixturesNot Available
Categories
UNII2VU8WT49WX
CAS number120313-91-9
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.

TargetKindPharmacological actionActionsOrganismUniProt ID
ProthrombinProteinyes
inhibitor
HumanP00734 details
Coagulation factor VProteinunknownNot AvailableHumanP12259 details
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot 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

ToxicityNot Available
Affected organismsNot Available
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions Not Available
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
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 LinksNot Available
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
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
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Taxonomy
DescriptionNot Available
KingdomOrganic Compounds
Super ClassOrganic Acids
ClassCarboxylic Acids and Derivatives
Sub ClassAmino Acids, Peptides, and Analogues
Direct ParentPeptides
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkNot Available
External DescriptorsNot 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 homeostasis, inflammation and wound healing.
Gene Name:
F2
Uniprot ID:
P00734
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
Molecular Weight:
251701.245 Da
Drug created on November 18, 2007 11:27 / Updated on March 13, 2017 14:04