DT-Web

DB00025 - Antihemophilic Factor


Identification
Name Antihemophilic Factor
Accession Number DB00025 (BIOD00029, BTD00029)
Type biotech
Description Human recombinant antihemophilic factor (AHF) or Factor VIII, 2332 residues, glycosylated, produced by CHO cells
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 264725.5000
Groups approved
Monoisotopic Weight Not Available
Pharmacology
Indication For the treatment of hemophilia A, von Willebrand disease and Factor XIII deficiency.
Mechanism of action Antihemophilic factor (AHF) is a protein found in normal plasma which is necessary for clot formation. The administration of AHF provides an increase in plasma levels of AHF and can temporarily correct the coagulation defect of patients with hemophilia A (classical hemophilia).
Absorption Not Available
Protein binding Not Available
Biotransformation Not Available
Route of elimination Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions Not Available
Food Interactions Not Available

Targets


Coagulation factor X
Name Coagulation factor X
Gene Name F10
Pharmacological action yes
Actions activator
References
  • 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
  • LUNDBLAD RL, DAVIE EW: THE ACTIVATION OF STUART FACTOR (FACTOR X) BY ACTIVATED ANTIHEMOPHILIC FACTOR (ACTIVATED FACTOR 8). Biochemistry. 1965 Jan;4:113-20. - Pubmed
  • Radnoff OD, Saito H: Inhibition of Hageman factor, plasma thromboplastin antecedent, thrombin and other clotting factors by phenylglyoxal hydrate (38500). Proc Soc Exp Biol Med. 1975 Jan;148(1):177-82. - Pubmed
  • Orthner CL: Characterization of proteases in AHF concentrates: effect on factor VIII:von Willebrand protein as assessed by high-pressure gel permeation chromatography. J Lab Clin Med. 1984 Nov;104(5):816-28. - Pubmed
  • Freedman J, Mody M, Lazarus AH, Dewar L, Song S, Blanchette VS, Garvey MB, Ofosu FA: Platelet activation and hypercoagulability following treatment with porcine factor VIII (HYATE:C). Am J Hematol. 2002 Mar;69(3):192-9. - Pubmed
DTHybrid score 2.0297
Coagulation factor IX
Name Coagulation factor IX
Gene Name F9
Pharmacological action yes
Actions cofactor
References
  • Hule V: [Factor IX inhibitor (antihemophilic factor B, PTC) in a woman] Vnitr Lek. 1975 Mar;21(3):274-7. - Pubmed
  • Yoshitake S, Schach BG, Foster DC, Davie EW, Kurachi K: Nucleotide sequence of the gene for human factor IX (antihemophilic factor B). Biochemistry. 1985 Jul 2;24(14):3736-50. - Pubmed
  • LUNDBLAD RL, DAVIE EW: THE ACTIVATION OF ANTIHEMOPHILIC FACTOR (FACTOR 8) BY ACTIVATED CHRISTMAS FACTOR (ACTIVATED FACTOR9 9). Biochemistry. 1964 Nov;3:1720-5. - Pubmed
  • Hoofnagle JH, Gerety RJ, Thiel J, Barker LF: The prevalence of hepatitis B surface antigen in commercially prepared plasma products. J Lab Clin Med. 1976 Jul;88(1):102-13. - Pubmed
  • Prince AM, Horowitz B, Brotman B, Huima T, Richardson L, van den Ende MC: Inactivation of hepatitis B and Hutchinson strain non-A, non-B hepatitis viruses by exposure to Tween 80 and ether. Vox Sang. 1984;46(1):36-43. - Pubmed
DTHybrid score 0.9985
von Willebrand factor
Name von Willebrand factor
Gene Name VWF
Pharmacological action yes
Actions binder
References
  • Shord SS, Lindley CM: Coagulation products and their uses. Am J Health Syst Pharm. 2000 Aug 1;57(15):1403-17; quiz 1418-20. - Pubmed
  • Lillicrap D, Poon MC, Walker I, Xie F, Schwartz BA: Efficacy and safety of the factor VIII/von Willebrand factor concentrate, haemate-P/humate-P: ristocetin cofactor unit dosing in patients with von Willebrand disease. Thromb Haemost. 2002 Feb;87(2):224-30. - Pubmed
  • Gill JC, Ewenstein BM, Thompson AR, Mueller-Velten G, Schwartz BA: Successful treatment of urgent bleeding in von Willebrand disease with factor VIII/VWF concentrate (Humate-P): use of the ristocetin cofactor assay (VWF:RCo) to measure potency and to guide therapy. Haemophilia. 2003 Nov;9(6):688-95. - Pubmed
  • Smith KJ, Lusher JM, Cohen AR, Salzman P: Initial clinical experience with a new pasteurized monoclonal antibody purified factor VIIIC. Semin Hematol. 1990 Apr;27(2 Suppl 2):25-9. - Pubmed
  • Altieri DC, Capitanio AM, Mannucci PM: von Willebrand factor contaminating porcine factor VIII concentrate (Hyate:C) causes platelet aggregation. Br J Haematol. 1986 Aug;63(4):703-11. - Pubmed
DTHybrid score 1.076
Phytanoyl-CoA dioxygenase, peroxisomal
Name Phytanoyl-CoA dioxygenase, peroxisomal
Gene Name PHYH
Pharmacological action unknown
Actions antagonist
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • 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
  • Chen C, Wang Q, Fang X, Xu Q, Chi C, Gu J: Roles of phytanoyl-CoA alpha-hydroxylase in mediating the expression of human coagulation factor VIII. J Biol Chem. 2001 Dec 7;276(49):46340-6. - Pubmed
DTHybrid score 0.9509
Asialoglycoprotein receptor 2
Name Asialoglycoprotein receptor 2
Gene Name ASGR2
Pharmacological action unknown
Actions binder
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • 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
  • Bovenschen N, Rijken DC, Havekes LM, van Vlijmen BJ, Mertens K: The B domain of coagulation factor VIII interacts with the asialoglycoprotein receptor. J Thromb Haemost. 2005 Jun;3(6):1257-65. - Pubmed
DTHybrid score 1.0768
78 kDa glucose-regulated protein
Name 78 kDa glucose-regulated protein
Gene Name HSPA5
Pharmacological action unknown
Actions chaperone
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • 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
  • Kaufman RJ, Pipe SW, Tagliavacca L, Swaroop M, Moussalli M: Biosynthesis, assembly and secretion of coagulation factor VIII. Blood Coagul Fibrinolysis. 1997 Dec;8 Suppl 2:S3-14. - Pubmed
DTHybrid score 1.0767
Calreticulin
Name Calreticulin
Gene Name CALR
Pharmacological action unknown
Actions chaperone
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • 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
  • Pipe SW, Morris JA, Shah J, Kaufman RJ: Differential interaction of coagulation factor VIII and factor V with protein chaperones calnexin and calreticulin. J Biol Chem. 1998 Apr 3;273(14):8537-44. - Pubmed
  • Srour MA, Grupp J, Aburubaiha Z, Albert T, Brondke H, Oldenburg J, Schwaab R: Modified expression of coagulation factor VIII by addition of a glycosylation site at the N terminus of the protein. Ann Hematol. 2007 Sep 26;. - Pubmed
  • Kaufman RJ, Pipe SW, Tagliavacca L, Swaroop M, Moussalli M: Biosynthesis, assembly and secretion of coagulation factor VIII. Blood Coagul Fibrinolysis. 1997 Dec;8 Suppl 2:S3-14. - Pubmed
  • Kaufman RJ, Pipe SW, Tagliavacca L, Swaroop M, Moussalli M: Biosynthesis, assembly and secretion of coagulation factor VIII. Blood Coagul Fibrinolysis. 1997 Dec;8 Suppl 2:S3-14. - Pubmed
DTHybrid score 1.063
Calnexin
Name Calnexin
Gene Name CANX
Pharmacological action unknown
Actions chaperone
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • 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
  • Pipe SW, Morris JA, Shah J, Kaufman RJ: Differential interaction of coagulation factor VIII and factor V with protein chaperones calnexin and calreticulin. J Biol Chem. 1998 Apr 3;273(14):8537-44. - Pubmed
  • Becker S, Simpson JC, Pepperkok R, Heinz S, Herder C, Grez M, Seifried E, Tonn T: Confocal microscopy analysis of native, full length and B-domain deleted coagulation factor VIII trafficking in mammalian cells. Thromb Haemost. 2004 Jul;92(1):23-35. - Pubmed
  • Srour MA, Grupp J, Aburubaiha Z, Albert T, Brondke H, Oldenburg J, Schwaab R: Modified expression of coagulation factor VIII by addition of a glycosylation site at the N terminus of the protein. Ann Hematol. 2007 Sep 26;. - Pubmed
  • Kaufman RJ, Pipe SW, Tagliavacca L, Swaroop M, Moussalli M: Biosynthesis, assembly and secretion of coagulation factor VIII. Blood Coagul Fibrinolysis. 1997 Dec;8 Suppl 2:S3-14. - Pubmed
DTHybrid score 1.1319
ERGIC-53 protein
Name ERGIC-53 protein
Gene Name LMAN1
Pharmacological action unknown
Actions chaperone
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • 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
  • Cunningham MA, Pipe SW, Zhang B, Hauri HP, Ginsburg D, Kaufman RJ: LMAN1 is a molecular chaperone for the secretion of coagulation factor VIII. J Thromb Haemost. 2003 Nov;1(11):2360-7. - Pubmed
  • Miao HZ, Sirachainan N, Palmer L, Kucab P, Cunningham MA, Kaufman RJ, Pipe SW: Bioengineering of coagulation factor VIII for improved secretion. Blood. 2004 May 1;103(9):3412-9. Epub 2004 Jan 15. - Pubmed
DTHybrid score 1.0766
Low-density lipoprotein receptor-related protein 1
Name Low-density lipoprotein receptor-related protein 1
Gene Name LRP1
Pharmacological action unknown
Actions modulator
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • 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
  • Franchini M, Montagnana M: Low-density lipoprotein receptor-related protein 1: new functions for an old molecule. Clin Chem Lab Med. 2011 Jun;49(6):967-70. Epub 2011 Mar 11. - Pubmed
DTHybrid score 1.1468
Multiple coagulation factor deficiency protein 2
Name Multiple coagulation factor deficiency protein 2
Gene Name MCFD2
Pharmacological action unknown
Actions modulator
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • 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
  • : - Pubmed
DTHybrid score 1.0774

Enzymes


Prothrombin
Name Prothrombin
Gene Name F2
Actions activator
References
  • Alberio L, Safa O, Clemetson KJ, Esmon CT, Dale GL: Surface expression and functional characterization of alpha-granule factor V in human platelets: effects of ionophore A23187, thrombin, collagen, and convulxin. Blood. 2000 Mar 1;95(5):1694-702. - Pubmed
  • Ratnoff OD, Lewis JH: Heckathorn's disease: variable functional dificiency of antihemophilic factor (factor VIII). Blood. 1975 Aug;46(2):161-73. - Pubmed
  • Anderson DM, Shelley S, Crick N, Buraglio M: No effect of the novel antidiabetic agent nateglinide on the pharmacokinetics and anticoagulant properties of warfarin in healthy volunteers. J Clin Pharmacol. 2002 Dec;42(12):1358-65. - Pubmed
  • Piet MP, Chin S, Prince AM, Brotman B, Cundell AM, Horowitz B: The use of tri(n-butyl)phosphate detergent mixtures to inactivate hepatitis viruses and human immunodeficiency virus in plasma and plasma's subsequent fractionation. Transfusion. 1990 Sep;30(7):591-8. - Pubmed
  • Lazarchick J, Ashby MA, Lazarchick JJ, Sens DA: Mechanism of factor VIII inactivation by human antibodies. IV. Antibody binding prevents factor VIII proteolysis by thrombin. Ann Clin Lab Sci. 1986 Nov-Dec;16(6):497-501. - Pubmed
DTHybrid score 2.1003
Vitamin K-dependent protein C
Name Vitamin K-dependent protein C
Gene Name PROC
Actions inactivator
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • 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
  • Bereczky Z, Kovacs KB, Muszbek L: Protein C and protein S deficiencies: similarities and differences between two brothers playing in the same game. Clin Chem Lab Med. 2010 Dec;48 Suppl 1:S53-66. Epub 2010 Nov 5. - Pubmed
DTHybrid score 1.2108

Predictions


Id Partner name Gene Name Score
5461 Coagulation factor IX F9 0.9985
1245 Vitamin K-dependent protein S PROS1 0.3269
3825 Tetranectin CLEC3B 0.2175
2111 Annexin A2 ANXA2 0.2174
3826 Keratin, type II cytoskeletal 8 KRT8 0.2174
1349 Plasminogen activator inhibitor 2 SERPINB2 0.1893
791 Urokinase plasminogen activator surface receptor PLAUR 0.1576
595 Fibrinogen alpha chain FGA 0.1509
267 Plasminogen activator inhibitor 1 SERPINE1 0.1489
448 Vitamin K-dependent gamma-carboxylase GGCX 0.1446
369 Coagulation factor VII F7 0.1407
234 Plasminogen PLG 0.1355
19 Coagulation factor VIII F8 0.1075
3176 Trypsin-1 PRSS1 0.1044
604 Vitamin K-dependent protein Z PROZ 0.084
4081 Vitamin K epoxide reductase complex subunit 1-like protein 1 VKORC1L1 0.0839
798 Osteocalcin BGLAP 0.0778
1547 Coagulation factor XI F11 0.077
243 Ribosyldihydronicotinamide dehydrogenase [quinone] NQO2 0.0692
309 Antithrombin-III SERPINC1 0.0533
787 Vitamin K epoxide reductase complex subunit 1 VKORC1 0.0519
3917 Methylenetetrahydrofolate reductase MTHFR 0.0466
6024 Cytochrome P450 1A1 CYP1A1 0.0434
6020 Aldehyde oxidase AOX1 0.043
2157 NAD(P)H dehydrogenase [quinone] 1 NQO1 0.0423
6034 Hydroxyindole O-methyltransferase ASMT 0.0393
6035 Nuclear receptor ROR-beta RORB 0.0393
6036 Eosinophil peroxidase EPX 0.0393
3962 Egl nine homolog 3 EGLN3 0.0392
3953 2-oxoglutarate and iron-dependent oxygenase domain containing 1 OGFOD1 0.0392
3948 Alpha-ketoglutarate-dependent dioxygenase alkB homolog 2 ALKBH2 0.0391
3956 Alpha-ketoglutarate-dependent dioxygenase alkB homolog 3 ALKBH3 0.0391
3946 Hypothetical protein DKFZp686H15154 OGFOD2 0.0391
3954 Egl nine homolog 2 EGLN2 0.0391
3966 Putative HIF-prolyl hydroxylase PH-4 P4HTM 0.0391
189 Solute carrier family 23 member 1 SLC23A1 0.0391
3935 Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 PLOD2 0.0391
3958 Jumonji/ARID domain-containing protein 1D KDM5D 0.0391
1757 Myeloperoxidase MPO 0.0391
3947 Xanthine dehydrogenase/oxidase XDH 0.0386
4200 Cytochrome P450 1A2 CYP1A2 0.0378
1074 Urokinase-type plasminogen activator PLAU 0.0362
765 Indoleamine 2,3-dioxygenase IDO1 0.0333
3964 Trimethyllysine dioxygenase, mitochondrial TMLHE 0.0306
3940 Gamma-butyrobetaine dioxygenase BBOX1 0.0305
97 Procollagen-lysine,2-oxoglutarate 5-dioxygenase 1 PLOD1 0.0305
3938 Procollagen-lysine,2-oxoglutarate 5-dioxygenase 3 PLOD3 0.0305
5718 Cytochrome P450 2A6 CYP2A6 0.0305
571 Melatonin receptor type 1A MTNR1A 0.03
362 Melatonin receptor type 1B MTNR1B 0.03
6013 Cytochrome P450 2E1 CYP2E1 0.0274
3943 Peptidyl-glycine alpha-amidating monooxygenase PAM 0.0272
3960 Egl nine homolog 1 EGLN1 0.0271
3951 Prolyl 3-hydroxylase 3 LEPREL2 0.0271
3949 Prolyl 3-hydroxylase 2 LEPREL1 0.0271
3945 Prolyl 3-hydroxylase 1 LEPRE1 0.0271
67 Prolyl 4-hydroxylase subunit alpha-1 P4HA1 0.0251
153 Dopamine beta-hydroxylase DBH 0.0251
2485 Hyaluronate lyase SP_0314 0.0223
3172 Hyaluronate lyase hylB 0.0223
2245 Xylose isomerase xylA 0.022
2253 Xylose isomerase xylA 0.022
2260 Xylose isomerase xylA 0.022
2431 Xylose isomerase xylA 0.022
6847 Lactase-phlorizin hydrolase LCT 0.0211
465 Calmodulin CALM1 0.0186
4757 Cytochrome P450 2C9 CYP2C9 0.0182
1898 Cytochrome P450 1B1 CYP1B1 0.0176
3851 Serine protease hepsin HPN 0.0171
3119 Fimbrial protein pilE1 0.0168
3811 Cytochrome P450 19A1 CYP19A1 0.0165
1719 Heparanase HPSE 0.0164
2058 P-selectin SELP 0.0156
136 Estrogen receptor ESR1 0.0154
6142 Solute carrier family 22 member 8 SLC22A8 0.0147
6182 Cytochrome P450 2J2 CYP2J2 0.0145
6016 Cytochrome P450 2C19 CYP2C19 0.0141
1334 Tissue factor pathway inhibitor TFPI 0.0132
6564 Prephenate dehydrogenase tyrA 0.0122
6240 Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 PIN1 0.0122
2139 Tissue factor F3 0.0111
4118 Cytochrome P450 3A5 CYP3A5 0.0102
2331 HTH-type transcriptional regulator qacR qacR 0.01
6461 HTH-type transcriptional regulator qacR qacR 0.01
6828 TetR family transcriptional repressor LfrR lfrR 0.0095
256 Tyrosyl-tRNA synthetase, cytoplasmic YARS 0.0093
3384 Macrophage migration inhibitory factor MIF 0.009
4512 Cytochrome P450 3A4 CYP3A4 0.0083
1588 Multidrug resistance protein 1 ABCB1 0.0079
4165 P2Y purinoceptor 2 P2RY2 0.0047
2654 Complement control protein C3L 0.0037
1959 Platelet factor 4 PF4 0.0035
3865 Serpin B6 SERPINB6 0.0035
1986 Ceruloplasmin CP 0.0035
430 Follicle-stimulating hormone receptor FSHR 0.0034
5766 NAD-dependent deacetylase sirtuin-5 SIRT5 0.0034
5455 Arylsulfatase A ARSA 0.0032
3833 Plasma serine protease inhibitor SERPINA5 0.0031
4604 Liver carboxylesterase 1 CES1 0.0031
2072 Endothelial protein C receptor PROCR 0.0031
46 Coagulation factor V F5 0.0031
814 Ryanodine receptor 1 RYR1 0.0029
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0027
6018 UDP-glucuronosyltransferase 1-9 UGT1A9 0.0027
2981 Phospholipase A2, membrane associated PLA2G2A 0.0026
2021 Thrombomodulin THBD 0.0026
6178 UDP-glucuronosyltransferase 2B7 UGT2B7 0.0025
723 Cytosolic phospholipase A2 PLA2G4A 0.0023
4924 Cytochrome P450 2C8 CYP2C8 0.0022
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