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coagulation factor IX

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Target not currently curated in GtoImmuPdb

Target id: 2364

Nomenclature: coagulation factor IX

Family: S1: Chymotrypsin

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 461 Xq27.1 F9 coagulation factor IX
Mouse - 471 X 33.5 cM F9 coagulation factor IX
Rat - 462 Xq36 F9 coagulation factor IX
Previous and Unofficial Names Click here for help
hemophilia B | plasma thromboplastic component | Cf9 | FIX | factor IX | christmas factor
Database Links Click here for help
Specialist databases
MEROPS S01.214 (Hs)
Other databases
Alphafold
BRENDA
CATH/Gene3D
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Enzyme Reaction Click here for help
EC Number: 3.4.21.22

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
compound 57 [PMID: 20121197] Small molecule or natural product Hs Inhibition 8.7 pIC50 6
pIC50 8.7 (IC50 2x10-9 M) [6]
Antibodies
Key to terms and symbols Click column headers to sort
Antibody Sp. Action Value Parameter Reference
emicizumab Peptide Approved drug Click here for species-specific activity table Hs Binding 5.8 pKd 5
pKd 5.8 (Kd 1.58x10-6 M) [5]
Description: Determined by surface plasmon resonance analysis.
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Mild hemophilia B
Synonyms: Hemophilia B; HEMB [OMIM: 306900] [Disease Ontology: DOID:12259]
Disease Ontology: DOID:12259
OMIM: 306900
Orphanet: ORPHA169799
Disease:  Moderately severe hemophilia B
Synonyms: Hemophilia B; HEMB [OMIM: 306900] [Disease Ontology: DOID:12259]
Disease Ontology: DOID:12259
OMIM: 306900
Orphanet: ORPHA169796
Disease:  Severe hemophilia B
Synonyms: Hemophilia B; HEMB [OMIM: 306900] [Disease Ontology: DOID:12259]
Disease Ontology: DOID:12259
OMIM: 306900
Orphanet: ORPHA169793
Disease:  Symptomatic form of hemophilia B in female carriers
Orphanet: ORPHA177929
Disease:  Thrombophilia, X-linked, due to factor IX defect
Synonyms: Thrombophilia [Disease Ontology: DOID:2452]
Disease Ontology: DOID:2452
OMIM: 300807
General Comments
Factor IX deficiency causes hemophilia B [1]. It is inhibited by endogenous antithrombin (SERPINC1) [2].

Recombinant factor IX (Nonafact®) is used to treat hemophilia B, however it is very rapidly cleared from the circulation. Peptide factor IX mimetics with enhanced biological properties are being developed to improve the effectiveness of hemophilia B prophylaxis. One such potent and long-acting factor IX mimetic is CB 2679d (ISU304), which is being developed by Catalyst Biosciences for subcutaneous administration (see Phase 1 proof-of-concept clinical trial NCT03186677) [4]. CB 2679d has been granted EMA orphan medicinal product designation (July 2017) [3].

References

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1. BIGGS R, DOUGLAS AS, MACFARLANE RG, DACIE JV, PITNEY WR, MERSKEY. (1952) Christmas disease: a condition previously mistaken for haemophilia. Br Med J, 2 (4799): 1378-82. [PMID:12997790]

2. Di Scipio RG, Kurachi K, Davie EW. (1978) Activation of human factor IX (Christmas factor). J Clin Invest, 61 (6): 1528-38. [PMID:659613]

3. EMA. CB 2679d orphan designation. Accessed on 28/09/2017. Modified on 28/09/2017. ema.europa.eu, http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/orphans/2017/07/human_orphan_001999.jsp&mid=WC0b01ac058001d12b

4. Hong S-B, Levy H, Jung JY, Park M, Seo AR, Seo SH, Madison E. (2016) Pharmacokinetics of Subcutaneously Administered CB2679d/ISU304 in Wild-Type and Hemophilia B Mice. Blood, 128: 1389.

5. Kitazawa T, Esaki K, Tachibana T, Ishii S, Soeda T, Muto A, Kawabe Y, Igawa T, Tsunoda H, Nogami K et al.. (2017) Factor VIIIa-mimetic cofactor activity of a bispecific antibody to factors IX/IXa and X/Xa, emicizumab, depends on its ability to bridge the antigens. Thromb Haemost, 117 (7): 1348-1357. [PMID:28451690]

6. Wang S, Beck R, Burd A, Blench T, Marlin F, Ayele T, Buxton S, Dagostin C, Malic M, Joshi R et al.. (2010) Structure based drug design: development of potent and selective factor IXa (FIXa) inhibitors. J Med Chem, 53 (4): 1473-82. [PMID:20121197]

How to cite this page

S1: Chymotrypsin: coagulation factor IX. Last modified on 24/01/2019. Accessed on 18/10/2021. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2364.