coagulation factor II, thrombin | S1: Chymotrypsin | IUPHAR/BPS Guide to PHARMACOLOGY

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coagulation factor II, thrombin

Target not currently curated in GtoImmuPdb

Target id: 2362

Nomenclature: coagulation factor II, thrombin

Family: S1: Chymotrypsin

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

Contents:

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 622 11p11.2 F2 coagulation factor II, thrombin
Mouse - 618 2 E1 F2 coagulation factor II
Rat - 617 3q24 F2 coagulation factor II
Previous and Unofficial Names
coagulation factor 2 | FII | Cf2 | thrombin | coagulation factor II (thrombin)
Database Links
Specialist databases
MEROPS S01.217 (Hs)
Other databases
BRENDA 3.4.21.5
CATH/Gene3D 4.10.140.10, 4.10.740.10
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
EC Number: 3.4.21.5

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 Value Parameter Reference
lepirudin Hs Inhibition 13.0 pKi 8
⤷ pKi 13.0 (Ki 1x10-13 M) [8]
desirudin Hs Inhibition 12.7 pKi 7
⤷ pKi 12.7 (Ki 2x10-13 M) [7]
Dup-714 Hs Inhibition 10.4 pKi 3
⤷ pKi 10.4 (Ki 4.1x10-11 M) [3]
Description: Affinity for thrombin active site.
AZ12971554 Hs Inhibition 9.5 pKi 1
⤷ pKi 9.5 (Ki 3x10-10 M) [1]
melagatran Hs Inhibition 8.7 pKi 4
⤷ pKi 8.7 (Ki 2x10-9 M) [4]
bivalirudin Hs Inhibition 8.6 pKi 9
⤷ pKi 8.6 (Ki 2.56x10-9 M) [9]
dabigatran Hs Inhibition 8.3 pKi 5
⤷ pKi 8.3 (Ki 4.5x10-9 M) [5]
Description: Binding affinity to human thrombin.
argatroban Hs Inhibition 7.7 pKi 6
⤷ pKi 7.7 (Ki 1.9x10-8 M) [6]
AR-H067637 Hs Inhibition 8.4 pIC50 2
⤷ pIC50 8.4 (IC50 4x10-9 M) [2]
Description: Assay using purified human α-thrombin
ximelagatran Hs Inhibition - -
⤷
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 3 GO processes
GO:0050900 leukocyte migration TAS
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
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 1 GO processes
GO:0050900 leukocyte migration TAS
Immuno Process:  Immune regulation
GO Annotations:  Associated to 2 GO processes
GO:0030449 regulation of complement activation TAS
GO:1900016 negative regulation of cytokine production involved in inflammatory response IDA
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 1 GO processes
GO:1900016 negative regulation of cytokine production involved in inflammatory response IDA
Clinically-Relevant Mutations and Pathophysiology
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. 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]

3. 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.

4. 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]

5. 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]

6. 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]

7. 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]

8. 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]

9. 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]

How to cite this page

S1: Chymotrypsin: coagulation factor II, thrombin. Last modified on 29/01/2016. Accessed on 30/09/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2362.