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coagulation factor II, thrombin

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Target not currently curated in GtoImmuPdb

Target id: 2362

Nomenclature: coagulation factor II, thrombin

Systematic Nomenclature: prothrombin

Family: Blood coagulation components, S1: Chymotrypsin

This target is also described as a ligand entry: thrombin; thrombin; thrombin

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 622 11p11.2 F2 coagulation factor II, thrombin
Mouse - 618 2 50.63 cM F2 coagulation factor II
Rat - 617 3q24 F2 coagulation factor II, thrombin
Previous and Unofficial Names Click here for help
coagulation factor II | Cf2 | coagulation factor 2 | coagulation factor II (thrombin) | FII | thrombin
Database Links Click here for help
Specialist databases
MEROPS S01.217 (Hs)
Other databases
Alphafold P00734 (Hs), P19221 (Mm), P18292 (Rn)
BRENDA 3.4.21.5
CATH/Gene3D 4.10.740.10, 4.10.140.10
ChEMBL Target CHEMBL204 (Hs), CHEMBL1075308 (Mm), CHEMBL3078 (Rn)
DrugBank Target P00734 (Hs), P00734 (Hs), P00734 (Hs)
Ensembl Gene ENSG00000180210 (Hs), ENSMUSG00000027249 (Mm), ENSRNOG00000016325 (Rn)
Entrez Gene 2147 (Hs), 14061 (Mm), 29251 (Rn)
Human Protein Atlas ENSG00000180210 (Hs)
KEGG Enzyme 3.4.21.5
KEGG Gene hsa:2147 (Hs), mmu:14061 (Mm), rno:29251 (Rn)
OMIM 176930 (Hs)
Orphanet ORPHA121671 (Hs)
Pharos P00734 (Hs)
RefSeq Nucleotide NM_000506 (Hs), NM_010168 (Mm), NM_022924 (Rn)
RefSeq Protein NP_000497 (Hs), NP_034298 (Mm), NP_075213 (Rn)
SynPHARM 78498 (in complex with melagatran)
UniProtKB P00734 (Hs), P19221 (Mm), P18292 (Rn)
Wikipedia F2 (Hs)
Enzyme Reaction Click here for help
EC Number: 3.4.21.5

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
lepirudin Peptide Approved drug Primary target of this compound Hs Inhibition 13.0 pKi 10,13
⤷ pKi 13.0 (Ki 1x10-13 M) [10,13]
desirudin Peptide Approved drug Primary target of this compound Hs Inhibition 12.7 pKi 4,9
⤷ pKi 12.7 (Ki 2x10-13 M) [4,9]
Dup-714 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 10.4 pKi 5
⤷ pKi 10.4 (Ki 4.1x10-11 M) [5]
Description: Affinity for thrombin active site.
AZ12971554 Small molecule or natural product Primary target of this compound Hs Inhibition 9.5 pKi 1
⤷ pKi 9.5 (Ki 3x10-10 M) [1]
melagatran Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Inhibition 8.7 pKi 6
⤷ pKi 8.7 (Ki 2x10-9 M) [6]
bivalirudin Peptide Approved drug Primary target of this compound Hs Inhibition 8.6 pKi 12,15
⤷ pKi 8.6 (Ki 2.56x10-9 M) [12,15]
dabigatran Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Inhibition 8.3 pKi 7,14
⤷ pKi 8.3 (Ki 4.5x10-9 M) Antithrombotic effects occur via inhibition of the activated form, factor IIa [7,14]
Description: Binding affinity to human thrombin.
argatroban Small molecule or natural product Approved drug Primary target of this compound Hs Inhibition 7.7 pKi 8,10
⤷ pKi 7.7 (Ki 1.9x10-8 M) [8,10]
WX-UK1 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.3 pKi 11
⤷ pKi 6.3 (Ki 5x10-7 M) [11]
AR-H067637 Small molecule or natural product Primary target of this compound Hs Inhibition 8.4 pIC50 3
⤷ pIC50 8.4 (IC50 4x10-9 M) [3]
Description: Assay using purified human α-thrombin
BAY 3389934 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.3 pIC50 2
⤷ pIC50 8.3 (IC50 5.3x10-9 M) Antithrombotic effect occurs via the inhibition of the activated form, IIa [2]
ximelagatran Small molecule or natural product Approved drug Hs - - -
⤷ Prodrug: no published quantitative data regarding inhibition of thrombin
Immuno Process Associations
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 1 GO processes
GO:1900016 negative regulation of cytokine production involved in inflammatory response IDA
Immuno Process:  Immune regulation
GO Annotations:  Associated to 1 GO processes
GO:1900016 negative regulation of cytokine production involved in inflammatory response IDA
Immuno Process:  Inflammation
GO Annotations:  Associated to 2 GO processes, IEA only
GO:1900016 negative regulation of cytokine production involved in inflammatory response IDA
click arrow to show/hide IEA associations
GO:0006953 acute-phase response IEA
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Cerebral sinovenous thrombosis
Orphanet: ORPHA329217
Disease:  Pregnancy loss, recurrent, susceptibility to, 2
OMIM: 614390
Disease:  Prothrombin deficiency, congenital
Synonyms: Congenital factor II deficiency [Orphanet: ORPHA325]
Prothrombin deficiency [Disease Ontology: DOID:2235]
Disease Ontology: DOID:2235
OMIM: 613679
Orphanet: ORPHA325
Disease:  Stroke, ischemic
Synonyms: Cerebral infarction
Cerebrovascular accident [Disease Ontology: DOID:3455]
Disease Ontology: DOID:3455
OMIM: 601367
Disease:  Thrombophilia due to thrombin defect
Synonyms: Thrombophilia [Disease Ontology: DOID:2452]
Disease Ontology: DOID:2452
OMIM: 188050

References

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1. AstraZeneca. AZ12971554. Accessed on 12/09/2014. Modified on 12/09/2014. astrazeneca.com, http://openinnovation.astrazeneca.com/what-we-offer/compound/az12971554/

2. Beck H, Mesch S, Vakalopoulos A, Pfaff N, Zimmermann S, Follmann M, Kersten E, Levilain G, Partikel K, Broehl AP et al.. (2023) Substituted s-alaninate derivatives. Patent number: US20230391761A1. Assignee: Bayer AG. Priority date: 11/08/2023. Publication date: 07/12/2023.

3. Deinum J, Mattsson C, Inghardt T, Elg M. (2009) Biochemical and pharmacological effects of the direct thrombin inhibitor AR-H067637. Thromb Haemost, 101 (6): 1051-9. [PMID:19492147]

4. Eriksson BI, Wille-Jørgensen P, Kälebo P, Mouret P, Rosencher N, Bösch P, Baur M, Ekman S, Bach D, Lindbratt S et al.. (1997) A comparison of recombinant hirudin with a low-molecular-weight heparin to prevent thromboembolic complications after total hip replacement. N Engl J Med, 337 (19): 1329-35. [PMID:9358126]

5. Galemmo RA Jr., Fevig JM, Carini DJ, Cacciola J, Wells BL, Hillyer GL, Buriak J Jr., Rossi KA, Stouten PFW, Alexander RS et al.. (1996) (N-acyl-N-alkyl)glycyl borolysine analogs: A new class of potent thrombin inhibitors. Bioorg Med Chem Lett, 6 (24): 2913–2918.

6. Gustafsson D, Antonsson T, Bylund R, Eriksson U, Gyzander E, Nilsson I, Elg M, Mattsson C, Deinum J, Pehrsson S et al.. (1998) Effects of melagatran, a new low-molecular-weight thrombin inhibitor, on thrombin and fibrinolytic enzymes. Thromb Haemost, 79 (1): 110-8. [PMID:9459334]

7. Hauel NH, Nar H, Priepke H, Ries U, Stassen JM, Wienen W. (2002) Structure-based design of novel potent nonpeptide thrombin inhibitors. J Med Chem, 45 (9): 1757-66. [PMID:11960487]

8. Imiya M, Matsuo T. (1997) Inhibition of collagen-induced platelet aggregation by argatroban in patients with acute cerebral infarction. Thromb Res, 88 (2): 245-50. [PMID:9361377]

9. Johnson PH, Sze P, Winant RC, Hudson D, Underhill P, Lazar JB, Olsen C, Almquist R. (1991) Structure-function and refolding studies of the thrombin-specific inhibitor hirudin. Haemostasis, 21 Suppl 1: 41-8. [PMID:1894196]

10. Seidel H, Kolde HJ. (2018) Monitoring of Argatroban and Lepirudin: What is the Input of Laboratory Values in "Real Life"?. Clin Appl Thromb Hemost, 24 (2): 287-294. [PMID:28320219]

11. Setyono-Han B, Stürzebecher J, Schmalix WA, Muehlenweg B, Sieuwerts AM, Timmermans M, Magdolen V, Schmitt M, Klijn JG, Foekens JA. (2005) Suppression of rat breast cancer metastasis and reduction of primary tumour growth by the small synthetic urokinase inhibitor WX-UK1. Thromb Haemost, 93 (4): 779-86. [PMID:15841327]

12. Stone GW, McLaurin BT, Cox DA, Bertrand ME, Lincoff AM, Moses JW, White HD, Pocock SJ, Ware JH, Feit F et al.. (2006) Bivalirudin for patients with acute coronary syndromes. N Engl J Med, 355 (21): 2203-16. [PMID:17124018]

13. Warkentin TE, Greinacher A, Craven S, Dewar L, Sheppard JA, Ofosu FA. (2005) Differences in the clinically effective molar concentrations of four direct thrombin inhibitors explain their variable prothrombin time prolongation. Thromb Haemost, 94 (5): 958-64. [PMID:16363236]

14. Wienen W, Stassen J-M, Priepke H, Ries UJ, Hauel N. (2007) In-vitro profile and ex-vivo anticoagulant activity of the direct thrombin inhibitor dabigatran and its orally active prodrug, dabigatran etexilate. Thrombosis and Haemostasis, 98 (01): 155-162. DOI: DOI: 10.1160/TH07-03-0183

15. Witting JI, Bourdon P, Brezniak DV, Maraganore JM, Fenton 2nd JW. (1992) Thrombin-specific inhibition by and slow cleavage of hirulog-1. Biochem J, 283 ( Pt 3): 737-43. [PMID:1290488]

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