Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTF0EGX)

• DTT Name: Coagulation factor VII (F7)
• Synonyms: Serum prothrombin conversion accelerator; SPCA; Proconvertin; Eptacog alfa
• Gene Name: F7
• DTT Type: Successful target; [1]
• BioChemical Class: Peptidase
• UniProt ID: FA7_HUMAN
• TTD ID: T43332
• EC Number: EC 3.4.21.21
• Sequence:
  MVSQALRLLCLLLGLQGCLAAGGVAKASGGETRDMPWKPGPHRVFVTQEEAHGVLHRRRR
  ANAFLEELRPGSLERECKEEQCSFEEAREIFKDAERTKLFWISYSDGDQCASSPCQNGGS
  CKDQLQSYICFCLPAFEGRNCETHKDDQLICVNENGGCEQYCSDHTGTKRSCRCHEGYSL
  LADGVSCTPTVEYPCGKIPILEKRNASKPQGRIVGGKVCPKGECPWQVLLLVNGAQLCGG
  TLINTIWVVSAAHCFDKIKNWRNLIAVLGEHDLSEHDGDEQSRRVAQVIIPSTYVPGTTN
  HDIALLRLHQPVVLTDHVVPLCLPERTFSERTLAFVRFSLVSGWGQLLDRGATALELMVL
  NVPRLMTQDCLQQSRKVGDSPNITEYMFCAGYSDGSKDSCKGDSGGPHATHYRGTWYLTG
  IVSWGQGCATVGHFGVYTRVSQYIEWLQKLMRSEPRPGVLLRAPFP
• Function: 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.
• KEGG Pathway: Complement and coagulation cascades (hsa04610)
• Reactome Pathway:
  Extrinsic Pathway of Fibrin Clot Formation (R-HSA-140834)
  Gamma-carboxylation of protein precursors (R-HSA-159740)
  Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus (R-HSA-159763)
  Removal of aminoterminal propeptides from gamma-carboxylated proteins (R-HSA-159782)
  BMAL1 (R-HSA-1368108)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Factor viia	DMZUW6P	Hemophilia	3B10.0	Approved	[1]

7 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BAX-817	DMB147A	Hemophilia	3B10.0	Phase 3	[2]
Vatreptacog alfa (activated)	DMANKTO	Bleeding disorder	GA20-GA21	Phase 3	[3]
Activated recombinant FVII-albumin fusion protein	DMKY9GI	Hemophilia	3B10.0	Phase 2/3	[4]
Recombinant factor VIIa PEGylated liposomal	DMY3TAD	Factor VII deficiency	3B14	Phase 1/2	[1]
CB-813	DMXQGKL	Hemophilia	3B10.0	Phase 1	[5]
Eptacog alfa	DMAQYRL	Hemophilia	3B10.0	Phase 1	[6]
F-7TG	DML4JXZ	Hemophilia	3B10.0	Phase 1	[1]

2 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BAY 86-6150	DM6R3WC	Hemophilia	3B10.0	Discontinued in Phase 2/3	[7]
RNAPc2	DME9V0I	Colorectal cancer	2B91.Z	Discontinued in Phase 2	[8]

7 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
4-(3,4-Diethoxy-benzylamino)-benzamidine	DMIZXYM	Discovery agent	N.A.	Investigative	[9]
4-(4-Benzyloxy-3-methoxy-benzylamino)-benzamidine	DME3PUT	Discovery agent	N.A.	Investigative	[9]
Factor-VIIa-XTEN	DMDWSH1	Hemophilia	3B10.0	Investigative	[1]
Fucose	DMAHMSV	N. A.	N. A.	Investigative	[10]
Human recombinant factor VIIa	DMARY2Z	Factor IX deficiency	3B11	Investigative	[1]
Long-acting Factor VII conjugate	DMAH0RZ	Bleeding disorder	GA20-GA21	Investigative	[1]
MOD-5023	DMKWBNA	Hemophilia	3B10.0	Investigative	[1]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Alzheimer's disease	8A00.0	Entorhinal cortex	2.52E-01	-0.03	-0.19
Rectal cancer	2C82	Rectal colon tissue	7.74E-02	0.45	1.11

References

• [1] URL: 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: 2363).
• [2] Clinical pipeline report, company report or official report of Baxter.
• [3] Recombinant factor VIIa analog (vatreptacog alfa [activated]) for treatment of joint bleeds in hemophilia patients with inhibitors: a randomized controlled trial. J Thromb Haemost. 2012 Jan;10(1):81-9.
• [4] ClinicalTrials.gov (NCT01542619) A Safety and Pharmacokinetics Study of a Recombinant Fusion Protein Linking Coagulation Factor VIIa With Albumin (rVIIa-FP) in Healthy Male Volunteers. U.S. National Institutes of Health.
• [5] Clinical pipeline report, company report or official report of Catalyst Biosciences.
• [6] Recombinant factor VIIa (eptacog alfa): a review of its use in congenital hemophilia with inhibitors, acquired hemophilia, and other congenital bleeding disorders. BioDrugs. 2008;22(2):121-36.
• [7] Bayer HealthCare and Maxygen Announce Hematology Agreement. U.S. Securities and Exchange Commission. July 2, 2008.
• [8] rNAPc2 inhibits colorectal cancer in mice through tissue factor. Clin Cancer Res. 2009 Jan 1;15(1):208-16.
• [9] Design of selective phenylglycine amide tissue factor/factor VIIa inhibitors. Bioorg Med Chem Lett. 2005 Feb 1;15(3):817-22.
• [10] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.