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Identification
Name Coagulation factor VIIa
Accession Number DB00036 (BIOD00006, BTD00006)
Type biotech
Groups approved
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 structure Db00036
Display: 3D Structure
Protein chemical formula C1972H3076N560O597S28
Protein average weight 45079.1000
Sequences 
>DB00036 sequence
ANAFLEELRPGSLERECKEEQCSFEEAREIFKDAERTKLFWISYSDGDQCASSPCQNGGS
CKDQLQSYICFCLPAFEGRNCETHKDDQLICVNENGGCEQYCSDHTGTKRSCRCHEGYSL
LADGVSCTPTVEYPCGKIPILEKRNASKPQGRIVGGKVCPKGECPWQVLLLVNGAQLCGG
TLINTIWVVSAAHCFDKIKNWRNLIAVLGEHDLSEHDGDEQSRRVAQVIIPSTYVPGTTN
HDIALLRLHQPVVLTDHVVPLCLPERTFSERTLAFVRFSLVSGWGQLLDRGATALELMVL
NVPRLMTQDCLQQSRKVGDSPNITEYMFCAGYSDGSKDSCKGDSGGPHATHYRGTWYLTG
IVSWGQGCATVGHFGVYTRVSQYIEWLQKLMRSEPRPGVLLRAPFP

FASTA
Synonyms
Coagulation factor VII precursor
Eptacog alfa
Proconvertin
Serum prothrombin conversion accelerator
SPCA
Salts Not Available
Brand names
Name Company
NovoSeven (Novo Nordisk)
Brand mixtures Not Available
Categories
  • Coagulants
  • Thrombotic Agents
CAS number 9001-25-6
Taxonomy
Kingdom Not Available
Classes Not Available
Substructures Not Available
Pharmacology
Indication For treatment of hemorrhagic complications in hemophilia A and B
Pharmacodynamics Used 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 action NovoSeven 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.
Absorption Not Available
Volume of distribution
  • 121 ± 30 mL/kg [adults]
  • 153 ± 29 mL/kg [children]
  • 280 to 290 mL/kg [congenital Factor VII deficiency]
Protein binding Not Available
Metabolism Not Available
Route of elimination Not Available
Half life Not 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]
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers Not Available
Packagers
Dosage forms
Form Route Strength
Injection, powder, lyophilized, for solution Intravenous bolus
Prices
Unit description Cost Unit
Novoseven 1200 mcg vial 1.64 USD vial
Novoseven 2400 mcg vial 1.64 USD vial
Novoseven 4800 mcg vial 1.64 USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State liquid
Experimental Properties
Property Value Source
melting point 58 °C Petersen, L.C. et al., Eur. J. Biochem 261: 124-129 (1999)
hydrophobicity -0.311 Not Available
isoelectric point 6.09 Not Available
References
Synthesis Reference Not 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
Resource Link
UniProt P08709 Link_out
Genbank M13232 Link_out
PharmGKB PA164748389 Link_out
RxList http://www.rxlist.com/cgi/generic3/novoseven.htm Link_out
Drugs.com http://www.drugs.com/cdi/coagulation-factor-viia-recombinant.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Factor_VII Link_out
ATC Codes Not Available
AHFS Codes Not Available
PDB Entries
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Coagulation factor X

Pharmacological action: unknown

Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting

Organism class: human
UniProt ID: P00742 Link_out
Gene: F10 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown

Plays an essential role in cell growth and maintenance of cell morphology

Organism class: human
UniProt ID: P05981 Link_out
Gene: HPN Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown

Inhibits factor X (X(a)) directly and, in a Xa-dependent way, inhibits VIIa/tissue factor activity, presumably by forming a quaternary Xa/LACI/VIIa/TF complex. It possesses an antithrombotic action and also the ability to associate with lipoproteins in plasma

Organism class: human
UniProt ID: P10646 Link_out
Gene: TFPI Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown

Mediates the vitamin K-dependent carboxylation of glutamate residues to calcium binding gamma-carboxyglutamate (Gla) residues with the concomitant convertion of the reduced hydroquinone form of vitamin K to vitamin K epoxide

Organism class: human
UniProt ID: P38435 Link_out
Gene: GGCX Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown

Initiates the extrinsic pathway of blood coagulation. Serine protease that circulates in the blood in a zymogen form. Factor VII is converted to factor VIIa by factor Xa, factor XIIa, factor IXa, or thrombin by minor proteolysis. In the presence of tissue factor and calcium ions, factor VIIa then converts factor X to factor Xa by limited proteolysis. Factor VIIa will also convert factor IX to factor IXa in the presence of tissue factor and calcium

Organism class: human
UniProt ID: P08709 Link_out
Gene: F7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown

Initiates blood coagulation by forming a complex with circulating factor VII or VIIa. The [TF:VIIa] complex activates factors IX or X by specific limited protolysis. TF plays a role in normal hemostasis by initiating the cell-surface assembly and propagation of the coagulation protease cascade

Organism class: human
UniProt ID: P13726 Link_out
Gene: F3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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