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Identification
NameCoagulation factor VIIa
Accession NumberDB00036  (BIOD00006, BTD00006)
Typebiotech
Groupsapproved
Description

Recombinant human coagulation Factor VIIa (rFVIIa), intended for promoting hemostasis by activating the extrinsic pathway of the coagulation cascade.1 NovoSeven is a vitamin K-dependent glycoprotein consisting of 406 amino acid residues. Cloned and expressed in hamster kidney cells, the protein is catalytically active in a two-chain form.

Protein structureDb00036
Protein chemical formulaC1972H3076N560O597S28
Protein average weight45079.1000
Sequences
>DB00036 sequence
ANAFLEELRPGSLERECKEEQCSFEEAREIFKDAERTKLFWISYSDGDQCASSPCQNGGS
CKDQLQSYICFCLPAFEGRNCETHKDDQLICVNENGGCEQYCSDHTGTKRSCRCHEGYSL
LADGVSCTPTVEYPCGKIPILEKRNASKPQGRIVGGKVCPKGECPWQVLLLVNGAQLCGG
TLINTIWVVSAAHCFDKIKNWRNLIAVLGEHDLSEHDGDEQSRRVAQVIIPSTYVPGTTN
HDIALLRLHQPVVLTDHVVPLCLPERTFSERTLAFVRFSLVSGWGQLLDRGATALELMVL
NVPRLMTQDCLQQSRKVGDSPNITEYMFCAGYSDGSKDSCKGDSGGPHATHYRGTWYLTG
IVSWGQGCATVGHFGVYTRVSQYIEWLQKLMRSEPRPGVLLRAPFP
Download FASTA Format
Synonyms
SynonymLanguageCode
Coagulation factor VII precursorNot AvailableNot Available
Eptacog alfaNot AvailableNot Available
ProconvertinNot AvailableNot Available
Serum prothrombin conversion acceleratorNot AvailableNot Available
SPCANot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
NovoSevenNovo Nordisk
Brand mixturesNot Available
CategoriesNot Available
CAS number9001-25-6
Taxonomy
KingdomOrganic Compounds
SuperclassOrganic Acids
ClassCarboxylic Acids and Derivatives
SubclassAmino Acids, Peptides, and Analogues
Direct parentPeptides
Alternative parentsNot Available
SubstituentsNot Available
Classification descriptionNot Available
Pharmacology
IndicationFor treatment of hemorrhagic complications in hemophilia A and B
PharmacodynamicsUsed in the treatment of bleeding episodes in hemophilia A or B. NovoSeven is recombinant Factor VIIa and, when complexed with tissue factor can activate coagulation Factor X to Factor Xa, as well as coagulation Factor IX to Factor IXa. Factor Xa, in complex with other factors, then converts prothrombin to thrombin, which leads to the formation of a hemostatic plug by converting fibrinogen to fibrin and thereby inducing local clotting.
Mechanism of actionNovoSeven activates the coagulation or clotting cascade by cleaving Factor IX and Factor X, which activates them and then leads to activation of thrombin and fibrin.
AbsorptionNot Available
Volume of distribution
  • 121 ± 30 mL/kg [adults]
  • 153 ± 29 mL/kg [children]
  • 280 to 290 mL/kg [congenital Factor VII deficiency]
Protein bindingNot Available
Metabolism
Route of eliminationNot Available
Half lifeNot Available
Clearance
  • 33 – 37 mL/h x kg [healthy]
  • 1375 +/- 396 mL/hr [severe hemophilia A male children]
  • 57.3 +/- 9.5 mL/hr/kg [severe hemophilia A male children]
  • 2767 +/- 385 mL/hr [severe hemophilia A men]
  • 37.6 +/- 13.1 mL/hr/kg [severe hemophilia A men]
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption Not Available Not Available
Blood Brain Barrier Not Available Not Available
Caco-2 permeable Not Available Not Available
P-glycoprotein substrate Not Available Not Available
P-glycoprotein inhibitor I Not Available Not Available
P-glycoprotein inhibitor II Not Available Not Available
Renal organic cation transporter Not Available Not Available
CYP450 2C9 substrate Not Available Not Available
CYP450 2D6 substrate Not Available Not Available
CYP450 3A4 substrate Not Available Not Available
CYP450 1A2 substrate Not Available Not Available
CYP450 2C9 substrate Not Available Not Available
CYP450 2D6 substrate Not Available Not Available
CYP450 2C19 substrate Not Available Not Available
CYP450 3A4 substrate Not Available Not Available
CYP450 inhibitory promiscuity Not Available Not Available
Ames test Not Available Not Available
Carcinogenicity Not Available Not Available
Biodegradation Not Available Not Available
Rat acute toxicity Not Available Not applicable
hERG inhibition (predictor I) Not Available Not Available
hERG inhibition (predictor II) Not Available Not Available
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionIntravenous bolus
Prices
Unit descriptionCostUnit
Novoseven 1200 mcg vial1.64USDvial
Novoseven 2400 mcg vial1.64USDvial
Novoseven 4800 mcg vial1.64USDvial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Stateliquid
Experimental Properties
PropertyValueSource
melting point58 °CPetersen, L.C. et al., Eur. J. Biochem 261: 124-129 (1999)
hydrophobicity-0.311Not Available
isoelectric point6.09Not Available
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  1. Blackshear PJ, Holloway PA, Alberti KG: Factors regulating amino acid release from extrasplanchnic tissues in the rat. Interactions of alanine and glutamine. Biochem J. 1975 Sep;150(3):379-87. Pubmed
  2. Roberts HR, Monroe DM, White GC: The use of recombinant factor VIIa in the treatment of bleeding disorders. Blood. 2004 Dec 15;104(13):3858-64. Epub 2004 Aug 24. Pubmed
  3. Kenet G, Walden R, Eldad A, Martinowitz U: Treatment of traumatic bleeding with recombinant factor VIIa. Lancet. 1999 Nov 27;354(9193):1879. Pubmed
  4. O’Connell KA, Wood JJ, Wise RP, Lozier JN, Braun MM: Thromboembolic adverse events after use of recombinant human coagulation factor VIIa. JAMA. 2006 Jan 18;295(3):293-8. Pubmed
  5. Mayer SA, Brun NC, Begtrup K, Broderick J, Davis S, Diringer MN, Skolnick BE, Steiner T: Recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med. 2005 Feb 24;352(8):777-85. Pubmed
External Links
ResourceLink
UniProtP08709
GenbankM13232
PharmGKBPA164748389
RxListhttp://www.rxlist.com/cgi/generic3/novoseven.htm
Drugs.comhttp://www.drugs.com/cdi/coagulation-factor-viia-recombinant.html
WikipediaFactor_VII
ATC CodesNot Available
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

1. Coagulation factor X

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Coagulation factor X P00742 Details

References:

  1. Malinvaud G: [Reflections on the use of PPSB fraction (Prothrombin-proconvertin-Stuart factor-antihemophilic factor B)] Transfusion (Paris). 1966;9(3):245-54. Pubmed
  2. BLATRIX C, SOULIER JP: [Preparation of a fraction rich in prothrombin, proconvertin, Stuart factor and antihemophilic factor B (P.P.B. fraction)] Pathol Biol (Paris). 1959 Dec;7:2477-86. Pubmed
  3. HERMANSKY F, VITEK J: The role of proconvertin and Stuart factor in the inactivation of tissue thromboplastin by serum. Experientia. 1960 Oct 15;16:455-6. Pubmed
  4. GAERTNER H, CAEN J: [FUNCTIONAL RELATION BETWEEN ERYTHROPLASTIN (ERYTHROCYTE COAGULANT FACTOR) AND PLASMA FACTORS: PROACCELERIN (V), PROCONVERTIN (VII) AND STUART FACTOR.] Acta Physiol Pol. 1964 Mar-Apr;15:237-43. Pubmed
  5. DIDISHEIM P, LOEB J, BLATRIX C, SOULIER JP: Preparation of a human plasma fraction rich in prothrombin, proconvertin, Stuart factor, and PTC and a study of its activity and toxicity in rabbits and man. J Lab Clin Med. 1959 Feb;53(2):322-30. Pubmed

2. Serine protease hepsin

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Serine protease hepsin P05981 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

3. Tissue factor pathway inhibitor

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Tissue factor pathway inhibitor P10646 Details

References:

  1. Mine S, Yamazaki T, Miyata T, Hara S, Kato H: Structural mechanism for heparin-binding of the third Kunitz domain of human tissue factor pathway inhibitor. Biochemistry. 2002 Jan 8;41(1):78-85. Pubmed
  2. Narita M, Bu G, Olins GM, Higuchi DA, Herz J, Broze GJ Jr, Schwartz AL: Two receptor systems are involved in the plasma clearance of tissue factor pathway inhibitor in vivo. J Biol Chem. 1995 Oct 20;270(42):24800-4. Pubmed
  3. Stassens P, Bergum PW, Gansemans Y, Jespers L, Laroche Y, Huang S, Maki S, Messens J, Lauwereys M, Cappello M, Hotez PJ, Lasters I, Vlasuk GP: Anticoagulant repertoire of the hookworm Ancylostoma caninum. Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):2149-54. Pubmed
  4. Lee AY, Vlasuk GP: Recombinant nematode anticoagulant protein c2 and other inhibitors targeting blood coagulation factor VIIa/tissue factor. J Intern Med. 2003 Oct;254(4):313-21. Pubmed
  5. Hansen CB, Pyke C, Petersen LC, Rao LV: Tissue factor-mediated endocytosis, recycling, and degradation of factor VIIa by a clathrin-independent mechanism not requiring the cytoplasmic domain of tissue factor. Blood. 2001 Mar 15;97(6):1712-20. Pubmed

4. Vitamin K-dependent gamma-carboxylase

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Vitamin K-dependent gamma-carboxylase P38435 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Bouwman CA, Van Dam E, Fase KM, Koppe JG, Seinen W, Thijssen HH, Vermeer C, Van den Berg M: Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin or 2,2’,4,4’,5,5’-hexachlorobiphenyl on vitamin K-dependent blood coagulation in male and female WAG/Rij-rats. Chemosphere. 1999 Feb;38(3):489-505. Pubmed

5. Coagulation factor VII

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Coagulation factor VII P08709 Details

References:

  1. Perera L, Darden TA, Pedersen LG: Probing the structural changes in the light chain of human coagulation factor VIIa due to tissue factor association. Biophys J. 1999 Jul;77(1):99-113. Pubmed
  2. Shapiro A: Inhibitor treatment: state of the art. Semin Hematol. 2001 Oct;38(4 Suppl 12):26-34. Pubmed
  3. Shapiro A: Inhibitor treatment: state of the art. Dis Mon. 2003 Jan;49(1):22-38. Pubmed
  4. Siddiqui MA, Scott LJ: Recombinant factor VIIa (Eptacog Alfa): a review of its use in congenital or acquired haemophilia and other congenital bleeding disorders. Drugs. 2005;65(8):1161-77. Pubmed
  5. Rizoli SB, Chughtai T: The emerging role of recombinant activated Factor VII (rFVIIa) in the treatment of blunt traumatic haemorrhage. Expert Opin Biol Ther. 2006 Jan;6(1):73-81. Pubmed

6. Tissue factor

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Tissue factor P13726 Details

References:

  1. HERMANSKY F, VITEK J: The role of proconvertin and Stuart factor in the inactivation of tissue thromboplastin by serum. Experientia. 1960 Oct 15;16:455-6. Pubmed
  2. Rogers KS, Barton CL, Benson PA, Green RA: Effects of single-dose L-asparaginase on coagulation values in healthy dogs and dogs with lymphoma. Am J Vet Res. 1992 Apr;53(4):580-4. Pubmed
  3. Christensen NJ: Measurements of some blood clotting factors using a centrifugal analyser (Multistat III). Scand J Clin Lab Invest. 1983 Oct;43(6):521-6. Pubmed

Comments
Drug created on June 13, 2005 07:24 / Updated on September 14, 2010 08:36