coagulation factor XI

Target id: 2360

Nomenclature: coagulation factor XI

Family: S1: Chymotrypsin

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for coagulation factor XI in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 625 4q35 F11 coagulation factor XI
Mouse - 624 8 B1.1 F11 coagulation factor XI
Rat - 556 16q11 F11 coagulation factor XI
Previous and Unofficial Names
Cf11 | FXI | plasma thromboplastin antecedent | PTA
Database Links
Specialist databases
MEROPS S01.213 (Hs)
Other databases
BRENDA
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Enzyme Reaction
EC Number: 3.4.21.27

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
alpha-ketothiazole analogue 36 Hs Inhibition 7.5 pIC50 2
pIC50 7.5 (IC50 3x10-8 M) [2]
Inhibitor Comments
BMS-962212 is a small molecule FXIa inhibitor - Ki 0.7 nM [4].
Clinically-Relevant Mutations and Pathophysiology
Disease:  Factor XI deficiency
Description: Hemophilia C is caused by autosomal recessive FXI deficiency and is associated with bleeding, although the bleeding pattern is unpredictable (or inconsistent) compared to hemophilias A and B. Bleeding events occur after surgery or injury, and trauma to the mucocutaneous lining of the oral or nasal cavities and the urinary tract is often the source of bleeding.
Synonyms: hemophilia C
plasma thromboplastin antecedent (PTA) deficiency
Rosenthal syndrome
Disease Ontology: DOID:2229
OMIM: 612416
Orphanet: ORPHA329
General Comments
FXI is the inactive proenzyme (or zymogen) of the plasma serine protease activated FXI (FXIa). FXI can be activated by FXIIa, thrombin, or FXIa. FXIa activates FIX to FIXa which in turn activates FX. FXI is produced in the liver and circulates as a homodimer.
FXIa contributes to thrombin generation and thrombus formation. Epidemiologic studies show that an elevated level of FXI is associated with an increased risk of venous thrombosis [3], and in contrast, FXI deficiency is associated with a reduced thrombosis risk [5]. These findings and results from experimental studies have linked FXI to thromboembolic disease, and suggest that FXI and/or FXIa inhibition may offer a novel approach for the development of antithrombotic therapeutics that would not impair normal hemostasis [1].

References

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1. Gailani D, Gruber A. (2016) Factor XI as a Therapeutic Target. Arterioscler. Thromb. Vasc. Biol., 36 (7): 1316-22. [PMID:27174099]

2. Maryanoff BE, Costanzo MJ. (2008) Inhibitors of proteases and amide hydrolases that employ an alpha-ketoheterocycle as a key enabling functionality. Bioorg. Med. Chem., 16 (4): 1562-95. [PMID:18053726]

3. Meijers JC, Tekelenburg WL, Bouma BN, Bertina RM, Rosendaal FR. (2000) High levels of coagulation factor XI as a risk factor for venous thrombosis. N. Engl. J. Med., 342 (10): 696-701. [PMID:10706899]

4. Pinto DJP, Orwat MJ, Smith 2nd LM, Quan ML, Lam PYS, Rossi KA, Apedo A, Bozarth JM, Wu Y, Zheng JJ et al.. (2017) Discovery of a Parenteral Small Molecule Coagulation Factor XIa Inhibitor Clinical Candidate (BMS-962212). J. Med. Chem., 60 (23): 9703-9723. [PMID:29077405]

5. Salomon O, Steinberg DM, Koren-Morag N, Tanne D, Seligsohn U. (2008) Reduced incidence of ischemic stroke in patients with severe factor XI deficiency. Blood, 111 (8): 4113-7. [PMID:18268095]

How to cite this page

S1: Chymotrypsin: coagulation factor XI. Last modified on 05/04/2018. Accessed on 22/07/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2360.