Target Information

Target General Infomation
Target ID
T14602
Former ID
TTDS00205
Target Name
Coagulation Factor VIIIa
Gene Name
F8
Synonyms
Factor VIIIa; F8
Target Type
Successful
Disease Atrial fibrillation [ICD9: 272, 427.31; ICD10: E78, I48]
Angina pectoris [ICD9: 413; ICD10: I20]
Blood clotting disorder [ICD9: 286; ICD10: D65-D69]
Factor VIII deficiency; Haemophilia A [ICD9:286; ICD10: D66]
Factor VIII deficiency [ICD10: D66]
Hemophilia [ICD9: 286; ICD10: D66-D68]
Hemophilia; Stroke [ICD9:286, 434.91, 437.6, 453, 671.5, 671.9; ICD10: D66-D68, I61-I63, I80-I82]
Hemophilia A [ICD9: 286; ICD10: D66]
Haemophilia A [ICD9: 286; ICD10: D66]
Severe sepsis; Cerebrovascular ischaemia [ICD9:995.91, 434.91; ICD10: A40-A41, I61-I63]
Von willebrand disease [ICD10: D68.0]
Unspecified [ICD code not available]
Function
Factor VIII, along with calcium and phospholipid, acts as a cofactor for factor IXa when it converts factor X to the activated form, factor Xa.
Target Validation
T14602
UniProt ID
P00451
Sequence
MQIELSTCFFLCLLRFCFSATRRYYLGAVELSWDYMQSDLGELPVDARFPPRVPKSFPFN
TSVVYKKTLFVEFTDHLFNIAKPRPPWMGLLGPTIQAEVYDTVVITLKNMASHPVSLHAV
GVSYWKASEGAEYDDQTSQREKEDDKVFPGGSHTYVWQVLKENGPMASDPLCLTYSYLSH
VDLVKDLNSGLIGALLVCREGSLAKEKTQTLHKFILLFAVFDEGKSWHSETKNSLMQDRD
AASARAWPKMHTVNGYVNRSLPGLIGCHRKSVYWHVIGMGTTPEVHSIFLEGHTFLVRNH
RQASLEISPITFLTAQTLLMDLGQFLLFCHISSHQHDGMEAYVKVDSCPEEPQLRMKNNE
EAEDYDDDLTDSEMDVVRFDDDNSPSFIQIRSVAKKHPKTWVHYIAAEEEDWDYAPLVLA
PDDRSYKSQYLNNGPQRIGRKYKKVRFMAYTDETFKTREAIQHESGILGPLLYGEVGDTL
LIIFKNQASRPYNIYPHGITDVRPLYSRRLPKGVKHLKDFPILPGEIFKYKWTVTVEDGP
TKSDPRCLTRYYSSFVNMERDLASGLIGPLLICYKESVDQRGNQIMSDKRNVILFSVFDE
NRSWYLTENIQRFLPNPAGVQLEDPEFQASNIMHSINGYVFDSLQLSVCLHEVAYWYILS
IGAQTDFLSVFFSGYTFKHKMVYEDTLTLFPFSGETVFMSMENPGLWILGCHNSDFRNRG
MTALLKVSSCDKNTGDYYEDSYEDISAYLLSKNNAIEPRSFSQNSRHPSTRQKQFNATTI
PENDIEKTDPWFAHRTPMPKIQNVSSSDLLMLLRQSPTPHGLSLSDLQEAKYETFSDDPS
PGAIDSNNSLSEMTHFRPQLHHSGDMVFTPESGLQLRLNEKLGTTAATELKKLDFKVSST
SNNLISTIPSDNLAAGTDNTSSLGPPSMPVHYDSQLDTTLFGKKSSPLTESGGPLSLSEE
NNDSKLLESGLMNSQESSWGKNVSSTESGRLFKGKRAHGPALLTKDNALFKVSISLLKTN
KTSNNSATNRKTHIDGPSLLIENSPSVWQNILESDTEFKKVTPLIHDRMLMDKNATALRL
NHMSNKTTSSKNMEMVQQKKEGPIPPDAQNPDMSFFKMLFLPESARWIQRTHGKNSLNSG
QGPSPKQLVSLGPEKSVEGQNFLSEKNKVVVGKGEFTKDVGLKEMVFPSSRNLFLTNLDN
LHENNTHNQEKKIQEEIEKKETLIQENVVLPQIHTVTGTKNFMKNLFLLSTRQNVEGSYD
GAYAPVLQDFRSLNDSTNRTKKHTAHFSKKGEEENLEGLGNQTKQIVEKYACTTRISPNT
SQQNFVTQRSKRALKQFRLPLEETELEKRIIVDDTSTQWSKNMKHLTPSTLTQIDYNEKE
KGAITQSPLSDCLTRSHSIPQANRSPLPIAKVSSFPSIRPIYLTRVLFQDNSSHLPAASY
RKKDSGVQESSHFLQGAKKNNLSLAILTLEMTGDQREVGSLGTSATNSVTYKKVENTVLP
KPDLPKTSGKVELLPKVHIYQKDLFPTETSNGSPGHLDLVEGSLLQGTEGAIKWNEANRP
GKVPFLRVATESSAKTPSKLLDPLAWDNHYGTQIPKEEWKSQEKSPEKTAFKKKDTILSL
NACESNHAIAAINEGQNKPEIEVTWAKQGRTERLCSQNPPVLKRHQREITRTTLQSDQEE
IDYDDTISVEMKKEDFDIYDEDENQSPRSFQKKTRHYFIAAVERLWDYGMSSSPHVLRNR
AQSGSVPQFKKVVFQEFTDGSFTQPLYRGELNEHLGLLGPYIRAEVEDNIMVTFRNQASR
PYSFYSSLISYEEDQRQGAEPRKNFVKPNETKTYFWKVQHHMAPTKDEFDCKAWAYFSDV
DLEKDVHSGLIGPLLVCHTNTLNPAHGRQVTVQEFALFFTIFDETKSWYFTENMERNCRA
PCNIQMEDPTFKENYRFHAINGYIMDTLPGLVMAQDQRIRWYLLSMGSNENIHSIHFSGH
VFTVRKKEEYKMALYNLYPGVFETVEMLPSKAGIWRVECLIGEHLHAGMSTLFLVYSNKC
QTPLGMASGHIRDFQITASGQYGQWAPKLARLHYSGSINAWSTKEPFSWIKVDLLAPMII
HGIKTQGARQKFSSLYISQFIIMYSLDGKKWQTYRGNSTGTLMVFFGNVDSSGIKHNIFN
PPIIARYIRLHPTHYSIRSTLRMELMGCDLNSCSMPLGMESKAISDAQITASSYFTNMFA
TWSPSKARLHLQGRSNAWRPQVNNPKEWLQVDFQKTMKVTGVTTQGVKSLLTSMYVKEFL
ISSSQDGHQWTLFFQNGKVKVFQGNQDSFTPVVNSLDPPLLTRYLRIHPQSWVHQIALRM
EVLGCEAQDLY
Drugs and Mode of Action
Drug(s) Drotrecogin alfa Drug Info Approved Severe sepsis; Cerebrovascular ischaemia [536361], [541868], [551871]
Eloctate Drug Info Approved Haemophilia A [533123]
Factor 8 Drug Info Approved Hemophilia [551871]
SK-NBP601 Drug Info Preregistration Hemophilia [549339]
BAY 94-9027 Drug Info Phase 3 Hemophilia; Stroke [548006]
N8-GP Drug Info Phase 3 Factor VIII deficiency; Haemophilia A [524756]
OBI-1 Drug Info Phase 3 Factor VIII deficiency [523623]
Plasma derived factor VIII PEGylated liposomal Drug Info Phase 3 Factor VIII deficiency [544080]
Recombinant von Willebrand factor/recombinant Factor VIII complex Drug Info Phase 3 Von willebrand disease [525418]
Turoctocog alfa Drug Info Phase 3 Hemophilia A [523733]
BAY 794980 Drug Info Phase 2 Unspecified [532058]
TB-402 Drug Info Phase 2 Atrial fibrillation [522492]
Modulator BAY 794980 Drug Info [532058]
BAY 94-9027 Drug Info [532784]
Eloctate Drug Info [533123], [551871]
Factor 8 Drug Info [543658]
Factor VIII-XTEN Drug Info [543658]
FIV vectors Drug Info [543658]
Full-length Factor VIII molecule, hemophilia Drug Info [543658]
Human recombinant factor VIII Drug Info [543658]
LA-N8 Drug Info [543658]
LG-889 Drug Info [543658]
Long-acting factor VIII Drug Info [543658]
N8-GP Drug Info [532228]
OBI-1 Drug Info [533120]
Plasma derived factor VIII PEGylated liposomal Drug Info [543658]
Recombinant von Willebrand factor/recombinant Factor VIII complex Drug Info [544151]
Simoctocog alfa Drug Info
SMaRT FVIII Drug Info [543658]
Turoctocog alfa Drug Info [533069]
Inhibitor Drotrecogin alfa Drug Info [537427]
GPG-290 Drug Info [543658]
IATX-FVIII Drug Info [543658]
SK-NBP601 Drug Info [551696]
Stimulator LG-888 Drug Info [543658]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Complement and coagulation cascades
PANTHER Pathway Blood coagulation
PathWhiz Pathway Coagulation
Reactome Platelet degranulation
Intrinsic Pathway of Fibrin Clot Formation
Common Pathway of Fibrin Clot Formation
COPII (Coat Protein 2) Mediated Vesicle Transport
Cargo concentration in the ER
WikiPathways Complement and Coagulation Cascades
Blood Clotting Cascade
Formation of Fibrin Clot (Clotting Cascade)
References
Ref 522492ClinicalTrials.gov (NCT00793234) Single Intravenous Administration of TB-402 for the Prophylaxis of Venous Thromboembolic Events (VTE) After Total Knee Replacement Surgery. U.S. National Institutes of Health.
Ref 523623ClinicalTrials.gov (NCT01434511) Study of Modified Recombinant Factor VIII (OBI-1) in Subjects With Congenital Hemophilia A. U.S. National Institutes of Health.
Ref 523733ClinicalTrials.gov (NCT01493778) Safety and Efficacy of Turoctocog Alfa in Prevention and Treatment of Bleeds in Previously Untreated Children With Haemophilia A. U.S. National Institutes of Health.
Ref 524756ClinicalTrials.gov (NCT02137850) Safety and Efficacy of Turoctocog Alfa Pegol (N8-GP) in Previously Untreated Patients With Haemophilia A. U.S. National Institutes of Health.
Ref 525418FcRn Rescues Recombinant Factor VIII Fc Fusion Protein from a VWF Independent FVIII Clearance Pathway in Mouse Hepatocytes. PLoS One. 2015 Apr 23;10(4):e0124930.
Ref 532058Efficacy and safety of prophylaxis with once-weekly BAY 79-4980 compared with thrice-weekly rFVIII-FS in haemophilia A patients. A randomised, active-controlled, double-blind study. Thromb Haemost. 2012 Nov;108(5):913-22.
Ref 5331232014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
Ref 536361Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. Epub 2007 Feb 20.
Ref 541868(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6788).
Ref 544080Recombinant factor VIII in the management of hemophilia A: current use and future promise. Ther Clin Risk Manag. 2009; 5: 391-402.
Ref 548006Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021112)
Ref 549339Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800035403)
Ref 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 532058Efficacy and safety of prophylaxis with once-weekly BAY 79-4980 compared with thrice-weekly rFVIII-FS in haemophilia A patients. A randomised, active-controlled, double-blind study. Thromb Haemost. 2012 Nov;108(5):913-22.
Ref 532228Enhancing the pharmacokinetic properties of recombinant factor VIII: first-in-human trial of glycoPEGylated recombinant factor VIII in patients with hemophilia A. J Thromb Haemost. 2013 Apr;11(4):670-8.
Ref 532784Phase I study of BAY 94-9027, a PEGylated B-domain-deleted recombinant factor VIII with an extended half-life, in subjects with hemophilia A. J Thromb Haemost. 2014 Apr;12(4):488-96.
Ref 533069The pharmacokinetics of a B-domain truncated recombinant factor VIII, turoctocog alfa (NovoEight?), in patients with hemophilia A. J Thromb Haemost. 2015 Mar;13(3):370-9.
Ref 533120Efficacy and safety of OBI-1, an antihaemophilic factor VIII (recombinant), porcine sequence, in subjects with acquired haemophilia A. Haemophilia. 2015 Mar;21(2):162-70.
Ref 5331232014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
Ref 537427Protein C in critical illness. Am J Health Syst Pharm. 2009 Jun 15;66(12):1089-96.
Ref 543658(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2607).
Ref 5441516 Factor VIII Concentrates, Factor VIII/von Willebrand Factor Concentrates, Factor IX Concentrates, Activated Prothrombin Complex Concentrates. Transfus Med Hemother. 2009 December; 36(6): 409-418.
Ref 551696Clinical pipeline report, company report or official report of SK Chemicals.
Ref 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015

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