Identification

Name
Drotrecogin alfa
Accession Number
DB00055  (BTD00068, BIOD00068)
Type
Biotech
Groups
Approved, Investigational, Withdrawn
Biologic Classification
Protein Based Therapies
Other protein based therapies
Description

Drotrecogin alfa is activated human protein C that is synthesized by recombinant DNA technology. It is a glycoprotein of approximately 55 kilodalton molecular weight, consisting of a heavy chain and a light chain linked by a disulfide bond. Drotrecogin alfa was withdrawn from the market after a major study indicated that it was not effective in improving outcomes in patients with sepsis.

Protein structure
Db00055
Protein chemical formula
C1786H2779N509O519S29
Protein average weight
55000.0 Da
Sequences
>Heavy chain
LIDGKMTRRGDSPWQVVLLDSKKKLACGAVLIHPSWVLTAAHCMDESKKLLVRLGEYDLR
RWEKWELDLDIKEVFVHPNYSKSTTDNDIALLHLAQPATLSQTIVPICLPDSGLAERELN
QAGQETLVTGWGYHSSREKEAKRNRTFVLNFIKIPVVPHNECSEVMSNMVSENMLCAGIL
GDRQDACEGDSGGPMVASFHGTWFLVGLVSWGEGCGLLHNYGVYTKVSRYLDWIHGHIRD
KEAPQKSWAP
>Light chain
SKHVDGDQCLVLPLEHPCASLCCGHGTCIXGIGSFSCDCRSGWEGRFCQREVSFLNCSLD
NGGCTHYCLEEVGWRRCSCAPGYKLGDDLLQCHPAVKFPCGRPWKRMEKKRSHL
Download FASTA Format
Synonyms
  • Activated protein C
  • Blood coagulation factor XIV (human)
  • Drotrecogin alfa (activated)
  • Drotrecogin alfa (activated), lyophilized
  • Drotrecogin alfa activated
  • Drotrecogin alfa, activated
  • Drotrecogin-alfa
  • Recombinant human activated protein C (rH-APC)
External IDs
LY203638
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Xigris (20mg/vial)Powder, for solution20 mgIntravenousEli Lilly & Co. Ltd.2003-03-252011-11-14Canada
Xigris (5mg/vial)Powder, for solution5 mgIntravenousEli Lilly & Co. Ltd.2003-02-202011-11-14Canada
Unapproved/Other Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
XigrisInjection, powder, for solution5 mgIntravenousEli Lilly Nederland B.V.2002-08-22Not applicableEu
XigrisInjection, powder, for solution20 mgIntravenousEli Lilly Nederland B.V.2002-08-22Not applicableEu
International/Other Brands
Xigris (Eli Lilly & Co)
Categories
UNII
JGH8MYC891
CAS number
98530-76-8

Pharmacology

Indication

For reduction of mortality in patients with severe sepsis.

Structured Indications
Not Available
Pharmacodynamics

Drotrecogin alfa is activated human protein C that is synthesized by recombinant DNA technology. It is a glycoprotein of approximately 55 kilodalton molecular weight, consisting of a heavy chain and a light chain linked by a disulfide bond. Drotrecogin alfa inhibits factor Va and VIIIa, thereby reducing the coagulability of blood.

Mechanism of action

Activated protein C combines with protein S on platelet surfaces and then degrades factor Va and factor VIIIa, thereby reducing blood coagulability.

TargetActionsOrganism
ACoagulation factor VIII
multitarget
Human
ACoagulation factor V
multitarget
Human
UPlasminogen activator inhibitor 1Not AvailableHuman
UThrombomodulinNot AvailableHuman
UVitamin K-dependent protein SNot AvailableHuman
UCeruloplasminNot AvailableHuman
UProthrombinNot AvailableHuman
UPlatelet factor 4Not AvailableHuman
UPlasma serine protease inhibitorNot AvailableHuman
USerpin B6Not AvailableHuman
UVitamin K-dependent gamma-carboxylaseNot AvailableHuman
UEndothelial protein C receptorNot AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life

5.5 hours (mammalian reticulocytes, in vitro).

Clearance
  • 40 L/hr [severe sepsis adults]
  • 30 +/- 8 L/hr [patients without sepsis undergoing hemodialysis]
  • 28 +/- 9 L/hr [heathy]
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AbciximabDrotrecogin alfa may increase the anticoagulant activities of Abciximab.Approved
AcenocoumarolDrotrecogin alfa may increase the anticoagulant activities of Acenocoumarol.Approved
Acetylsalicylic acidThe risk or severity of adverse effects can be increased when Acetylsalicylic acid is combined with Drotrecogin alfa.Approved, Vet Approved
AloxiprinThe risk or severity of adverse effects can be increased when Aloxiprin is combined with Drotrecogin alfa.Experimental
AlprostadilAlprostadil may increase the anticoagulant activities of Drotrecogin alfa.Approved, Investigational
Aminosalicylic AcidThe risk or severity of adverse effects can be increased when Aminosalicylic Acid is combined with Drotrecogin alfa.Approved
AnagrelideAnagrelide may increase the anticoagulant activities of Drotrecogin alfa.Approved
AncrodDrotrecogin alfa may increase the anticoagulant activities of Ancrod.Investigational
AndrographolideAndrographolide may increase the anticoagulant activities of Drotrecogin alfa.Investigational
Antithrombin III humanDrotrecogin alfa may increase the anticoagulant activities of Antithrombin III human.Approved
ApixabanDrotrecogin alfa may increase the anticoagulant activities of Apixaban.Approved
AprotininThe therapeutic efficacy of Drotrecogin alfa can be decreased when used in combination with Aprotinin.Approved, Withdrawn
ArdeparinDrotrecogin alfa may increase the anticoagulant activities of Ardeparin.Approved, Withdrawn
ArgatrobanDrotrecogin alfa may increase the anticoagulant activities of Argatroban.Approved, Investigational
AzelastineAzelastine may increase the anticoagulant activities of Drotrecogin alfa.Approved
BalsalazideThe risk or severity of adverse effects can be increased when Balsalazide is combined with Drotrecogin alfa.Approved, Investigational
BecaplerminDrotrecogin alfa may increase the anticoagulant activities of Becaplermin.Approved, Investigational
BeraprostBeraprost may increase the anticoagulant activities of Drotrecogin alfa.Investigational
BivalirudinDrotrecogin alfa may increase the anticoagulant activities of Bivalirudin.Approved, Investigational
BuflomedilBuflomedil may increase the anticoagulant activities of Drotrecogin alfa.Experimental
ButylphthalideButylphthalide may increase the anticoagulant activities of Drotrecogin alfa.Investigational
CangrelorCangrelor may increase the anticoagulant activities of Drotrecogin alfa.Approved
Carbaspirin calciumThe risk or severity of adverse effects can be increased when Carbaspirin calcium is combined with Drotrecogin alfa.Experimental
CertoparinDrotrecogin alfa may increase the anticoagulant activities of Certoparin.Approved
CilostazolCilostazol may increase the anticoagulant activities of Drotrecogin alfa.Approved
Citric AcidDrotrecogin alfa may increase the anticoagulant activities of Citric Acid.Nutraceutical, Vet Approved
ClopidogrelClopidogrel may increase the anticoagulant activities of Drotrecogin alfa.Approved, Nutraceutical
CloricromenCloricromen may increase the anticoagulant activities of Drotrecogin alfa.Experimental
Dabigatran etexilateDrotrecogin alfa may increase the anticoagulant activities of Dabigatran etexilate.Approved
DalteparinDrotrecogin alfa may increase the anticoagulant activities of Dalteparin.Approved
DanaparoidDrotrecogin alfa may increase the anticoagulant activities of Danaparoid.Approved, Withdrawn
DarexabanDrotrecogin alfa may increase the anticoagulant activities of Darexaban.Investigational
DefibrotideDefibrotide may increase the anticoagulant activities of Drotrecogin alfa.Approved, Investigational
dersalazineThe risk or severity of adverse effects can be increased when dersalazine is combined with Drotrecogin alfa.Investigational
DesirudinDrotrecogin alfa may increase the anticoagulant activities of Desirudin.Approved
DextranDrotrecogin alfa may increase the anticoagulant activities of Dextran.Approved, Vet Approved
Dextran 40Drotrecogin alfa may increase the anticoagulant activities of Dextran 40.Approved
Dextran 70Drotrecogin alfa may increase the anticoagulant activities of Dextran 70.Approved
Dextran 75Drotrecogin alfa may increase the anticoagulant activities of Dextran 75.Approved
DicoumarolDrotrecogin alfa may increase the anticoagulant activities of Dicoumarol.Approved
DiflunisalThe risk or severity of adverse effects can be increased when Diflunisal is combined with Drotrecogin alfa.Approved
DipyridamoleDipyridamole may increase the anticoagulant activities of Drotrecogin alfa.Approved
Edetic AcidDrotrecogin alfa may increase the anticoagulant activities of Edetic Acid.Approved, Vet Approved
EdoxabanDrotrecogin alfa may increase the anticoagulant activities of Edoxaban.Approved
EnoxaparinDrotrecogin alfa may increase the anticoagulant activities of Enoxaparin.Approved
EpinastineEpinastine may increase the anticoagulant activities of Drotrecogin alfa.Approved, Investigational
EplivanserinEplivanserin may increase the anticoagulant activities of Drotrecogin alfa.Investigational
eplivanserineeplivanserine may increase the anticoagulant activities of Drotrecogin alfa.Investigational
EpoprostenolEpoprostenol may increase the anticoagulant activities of Drotrecogin alfa.Approved
EptifibatideEptifibatide may increase the anticoagulant activities of Drotrecogin alfa.Approved, Investigational
Ethyl biscoumacetateDrotrecogin alfa may increase the anticoagulant activities of Ethyl biscoumacetate.Withdrawn
Ferulic acidDrotrecogin alfa may increase the anticoagulant activities of Ferulic acid.Experimental
FluindioneDrotrecogin alfa may increase the anticoagulant activities of Fluindione.Investigational
FondaparinuxDrotrecogin alfa may increase the anticoagulant activities of Fondaparinux.Investigational
Fondaparinux sodiumDrotrecogin alfa may increase the anticoagulant activities of Fondaparinux sodium.Approved, Investigational
GabexateDrotrecogin alfa may increase the anticoagulant activities of Gabexate.Investigational
GuacetisalThe risk or severity of adverse effects can be increased when Guacetisal is combined with Drotrecogin alfa.Experimental
Hemoglobin crosfumarilThe risk or severity of adverse effects can be increased when Hemoglobin crosfumaril is combined with Drotrecogin alfa.Experimental
HeparinDrotrecogin alfa may increase the anticoagulant activities of Heparin.Approved, Investigational
HydroxytyrosolHydroxytyrosol may increase the anticoagulant activities of Drotrecogin alfa.Investigational
IbudilastIbudilast may increase the anticoagulant activities of Drotrecogin alfa.Approved, Investigational
Icosapent ethylIcosapent ethyl may increase the anticoagulant activities of Drotrecogin alfa.Approved, Nutraceutical
IdraparinuxDrotrecogin alfa may increase the anticoagulant activities of Idraparinux.Investigational
IfenprodilIfenprodil may increase the anticoagulant activities of Drotrecogin alfa.Approved, Withdrawn
IfetrobanIfetroban may increase the anticoagulant activities of Drotrecogin alfa.Investigational
IloprostIloprost may increase the anticoagulant activities of Drotrecogin alfa.Approved, Investigational
IndobufenIndobufen may increase the anticoagulant activities of Drotrecogin alfa.Investigational
KetanserinKetanserin may increase the anticoagulant activities of Drotrecogin alfa.Investigational
LepirudinDrotrecogin alfa may increase the anticoagulant activities of Lepirudin.Approved
LetaxabanDrotrecogin alfa may increase the anticoagulant activities of Letaxaban.Investigational
LimaprostThe risk or severity of adverse effects can be increased when Limaprost is combined with Drotrecogin alfa.Approved
LinsidomineLinsidomine may increase the anticoagulant activities of Drotrecogin alfa.Experimental
MelagatranDrotrecogin alfa may increase the anticoagulant activities of Melagatran.Experimental
MesalazineThe risk or severity of adverse effects can be increased when Mesalazine is combined with Drotrecogin alfa.Approved
MilrinoneMilrinone may increase the anticoagulant activities of Drotrecogin alfa.Approved
NadroparinDrotrecogin alfa may increase the anticoagulant activities of Nadroparin.Approved
NafamostatDrotrecogin alfa may increase the anticoagulant activities of Nafamostat.Approved, Investigational
NaftopidilNaftopidil may increase the anticoagulant activities of Drotrecogin alfa.Investigational
NimesulideNimesulide may increase the anticoagulant activities of Drotrecogin alfa.Approved, Withdrawn
NitroaspirinThe risk or severity of adverse effects can be increased when Nitroaspirin is combined with Drotrecogin alfa.Investigational
OlsalazineThe risk or severity of adverse effects can be increased when Olsalazine is combined with Drotrecogin alfa.Approved
OtamixabanDrotrecogin alfa may increase the anticoagulant activities of Otamixaban.Investigational
Pentosan PolysulfateDrotrecogin alfa may increase the anticoagulant activities of Pentosan Polysulfate.Approved
PentoxifyllinePentoxifylline may increase the anticoagulant activities of Drotrecogin alfa.Approved, Investigational
PhenindioneDrotrecogin alfa may increase the anticoagulant activities of Phenindione.Approved
PhenprocoumonDrotrecogin alfa may increase the anticoagulant activities of Phenprocoumon.Approved
PicotamidePicotamide may increase the anticoagulant activities of Drotrecogin alfa.Experimental
PrasugrelPrasugrel may increase the anticoagulant activities of Drotrecogin alfa.Approved
Protein CDrotrecogin alfa may increase the anticoagulant activities of Protein C.Approved
Protein S humanDrotrecogin alfa may increase the anticoagulant activities of Protein S human.Approved
ProtocatechualdehydeDrotrecogin alfa may increase the anticoagulant activities of Protocatechualdehyde.Approved
RamatrobanRamatroban may increase the anticoagulant activities of Drotrecogin alfa.Investigational
ResveratrolResveratrol may increase the anticoagulant activities of Drotrecogin alfa.Experimental, Investigational
ReviparinDrotrecogin alfa may increase the anticoagulant activities of Reviparin.Approved
RidogrelRidogrel may increase the anticoagulant activities of Drotrecogin alfa.Approved
RivaroxabanDrotrecogin alfa may increase the anticoagulant activities of Rivaroxaban.Approved
Salicylic acidThe risk or severity of adverse effects can be increased when Salicylic acid is combined with Drotrecogin alfa.Approved, Vet Approved
SarpogrelateSarpogrelate may increase the anticoagulant activities of Drotrecogin alfa.Investigational
SevofluraneSevoflurane may increase the anticoagulant activities of Drotrecogin alfa.Approved, Vet Approved
SRT501SRT501 may increase the anticoagulant activities of Drotrecogin alfa.Investigational
SulodexideDrotrecogin alfa may increase the anticoagulant activities of Sulodexide.Approved, Investigational
TesmilifeneTesmilifene may increase the anticoagulant activities of Drotrecogin alfa.Investigational
TiclopidineTiclopidine may increase the anticoagulant activities of Drotrecogin alfa.Approved
TirofibanTirofiban may increase the anticoagulant activities of Drotrecogin alfa.Approved
TranilastTranilast may increase the anticoagulant activities of Drotrecogin alfa.Approved, Investigational
TrapidilTrapidil may increase the anticoagulant activities of Drotrecogin alfa.Approved
TreprostinilThe risk or severity of adverse effects can be increased when Drotrecogin alfa is combined with Treprostinil.Approved, Investigational
TriflusalTriflusal may increase the anticoagulant activities of Drotrecogin alfa.Approved
TroxerutinDrotrecogin alfa may increase the anticoagulant activities of Troxerutin.Investigational
VorapaxarVorapaxar may increase the anticoagulant activities of Drotrecogin alfa.Approved
WarfarinDrotrecogin alfa may increase the anticoagulant activities of Warfarin.Approved
XimelagatranDrotrecogin alfa may increase the anticoagulant activities of Ximelagatran.Approved, Investigational, Withdrawn
Food Interactions
Not Available

References

Synthesis Reference
Not Available
General References
Not Available
External Links
UniProt
P04070
Genbank
M11228
Therapeutic Targets Database
DAP000151
PharmGKB
PA131548935
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Drotrecogin_alfa
ATC Codes
B01AD10 — Drotrecogin alfa (activated)
AHFS Codes
  • 20:12.20
PDB Entries
FDA label
Download (241 KB)
MSDS
Not Available

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedTreatmentLung Inflammation1
2CompletedTreatmentEnd Stage Renal Disease (ESRD)1
2CompletedTreatmentSepsis / Shock, Septic1
2CompletedTreatmentSevere Sepsis1
2CompletedTreatmentSubmassive Pulmonary Embolism1
2TerminatedTreatmentRespiratory Distress Syndrome, Adult1
2TerminatedTreatmentStrokes1
3CompletedTreatmentArterial Hypotension / Sepsis1
3CompletedTreatmentSepsis3
4CompletedTreatmentAcute Pancreatitis (AP)1
4CompletedTreatmentHematopoietic Stem Cell Transplantation (HSCT) / Infection NOS / Neoplasms, Hematologic / Sepsis1
4CompletedTreatmentSepsis2
4CompletedTreatmentSepsis / Shock, Septic1
4CompletedTreatmentSevere Sepsis1
4CompletedTreatmentShock, Septic1
Not AvailableCompletedNot AvailableSepsis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Dosage forms
FormRouteStrength
Injection, powder, for solutionIntravenous20 mg
Injection, powder, for solutionIntravenous5 mg
Powder, for solutionIntravenous20 mg
Powder, for solutionIntravenous5 mg
Prices
Unit descriptionCostUnit
Xigris 20 mg vial1481.66USD vial
Xigris 5 mg vial370.42USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2139468No2007-08-212015-01-03Canada
CA2036894No2002-01-152011-02-22Canada

Properties

State
Liquid
Experimental Properties
PropertyValueSource
hydrophobicity-0.291Not Available
isoelectric point6.78Not Available

Taxonomy

Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Multitarget
General Function
Oxidoreductase activity
Specific Function
Factor VIII, along with calcium and phospholipid, acts as a cofactor for factor IXa when it converts factor X to the activated form, factor Xa.
Gene Name
F8
Uniprot ID
P00451
Uniprot Name
Coagulation factor VIII
Molecular Weight
267007.42 Da
References
  1. Geng JP, Castellino FJ: Properties of a recombinant chimeric protein in which the gamma-carboxyglutamic acid and helical stack domains of human anticoagulant protein C are replaced by those of human coagulation factor VII. Thromb Haemost. 1997 May;77(5):926-33. [PubMed:9184404]
  2. Colin G, Annane D: Corticosteroids and human recombinant activated protein C for septic shock. Clin Chest Med. 2008 Dec;29(4):705-12, x. doi: 10.1016/j.ccm.2008.06.009. [PubMed:18954704]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Multitarget
General Function
Copper ion binding
Specific Function
Central regulator of hemostasis. It serves as a critical cofactor for the prothrombinase activity of factor Xa that results in the activation of prothrombin to thrombin.
Gene Name
F5
Uniprot ID
P12259
Uniprot Name
Coagulation factor V
Molecular Weight
251701.245 Da
References
  1. Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, Steingrub JS, Garber GE, Helterbrand JD, Ely EW, Fisher CJ Jr: Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med. 2001 Mar 8;344(10):699-709. [PubMed:11236773]
  2. Kanji S, Devlin JW, Piekos KA, Racine E: Recombinant human activated protein C, drotrecogin alfa (activated): a novel therapy for severe sepsis. Pharmacotherapy. 2001 Nov;21(11):1389-402. [PubMed:11714212]
  3. Lyseng-Williamson KA, Perry CM: Drotrecogin alfa (activated). Drugs. 2002;62(4):617-30; discussion 631-2. [PubMed:11893230]
  4. Joyce DE, Grinnell BW: Recombinant human activated protein C attenuates the inflammatory response in endothelium and monocytes by modulating nuclear factor-kappaB. Crit Care Med. 2002 May;30(5 Suppl):S288-93. [PubMed:12004250]
  5. Poe K: Drotrecogin alfa (activated) approved for treatment of severe sepsis. J Am Pharm Assoc (Wash). 2002 May-Jun;42(3):520-2. [PubMed:12030642]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Serine-type endopeptidase inhibitor activity
Specific Function
Serine protease inhibitor. This inhibitor acts as 'bait' for tissue plasminogen activator, urokinase, protein C and matriptase-3/TMPRSS7. Its rapid interaction with PLAT may function as a major con...
Gene Name
SERPINE1
Uniprot ID
P05121
Uniprot Name
Plasminogen activator inhibitor 1
Molecular Weight
45059.695 Da
References
  1. Carr ME: Diabetes mellitus: a hypercoagulable state. J Diabetes Complications. 2001 Jan-Feb;15(1):44-54. [PubMed:11259926]
  2. Cerchiara E, Tirindelli MC, Giannetti B, Dicuonzo G, Avvisati G: [The numerous properties of the anticoagulant protein C]. Clin Ter. 2007 Mar-Apr;158(2):181-7. [PubMed:17566522]
  3. Idell S: Endothelium and disordered fibrin turnover in the injured lung: newly recognized pathways. Crit Care Med. 2002 May;30(5 Suppl):S274-80. [PubMed:12004248]
  4. Dhainaut JF, Yan SB, Margolis BD, Lorente JA, Russell JA, Freebairn RC, Spapen HD, Riess H, Basson B, Johnson G 3rd, Kinasewitz GT: Drotrecogin alfa (activated) (recombinant human activated protein C) reduces host coagulopathy response in patients with severe sepsis. Thromb Haemost. 2003 Oct;90(4):642-53. [PubMed:14515185]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Transmembrane signaling receptor activity
Specific Function
Thrombomodulin is a specific endothelial cell receptor that forms a 1:1 stoichiometric complex with thrombin. This complex is responsible for the conversion of protein C to the activated protein C ...
Gene Name
THBD
Uniprot ID
P07204
Uniprot Name
Thrombomodulin
Molecular Weight
60328.72 Da
References
  1. Gresele P, Agnelli G: Novel approaches to the treatment of thrombosis. Trends Pharmacol Sci. 2002 Jan;23(1):25-32. [PubMed:11804648]
  2. Pineda AO, Chen ZW, Caccia S, Cantwell AM, Savvides SN, Waksman G, Mathews FS, Di Cera E: The anticoagulant thrombin mutant W215A/E217A has a collapsed primary specificity pocket. J Biol Chem. 2004 Sep 17;279(38):39824-8. Epub 2004 Jul 13. [PubMed:15252033]
  3. McCachren SS, Diggs J, Weinberg JB, Dittman WA: Thrombomodulin expression by human blood monocytes and by human synovial tissue lining macrophages. Blood. 1991 Dec 15;78(12):3128-32. [PubMed:1660324]
  4. Shirai T, Shiojiri S, Ito H, Yamamoto S, Kusumoto H, Deyashiki Y, Maruyama I, Suzuki K: Gene structure of human thrombomodulin, a cofactor for thrombin-catalyzed activation of protein C. J Biochem. 1988 Feb;103(2):281-5. [PubMed:2836377]
  5. Boffa MC, Burke B, Haudenschild C: [Different localization of thrombomodulin]. Ann Biol Clin (Paris). 1987;45(2):191-7. [PubMed:3039877]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Endopeptidase inhibitor activity
Specific Function
Anticoagulant plasma protein; it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. It helps to prevent coagulation and stimulating fibrinolysis.
Gene Name
PROS1
Uniprot ID
P07225
Uniprot Name
Vitamin K-dependent protein S
Molecular Weight
75121.905 Da
References
  1. Cvirn G, Gallistl S, Koestenberger M, Kutschera J, Leschnik B, Muntean W: Alpha 2-macroglobulin enhances prothrombin activation and thrombin potential by inhibiting the anticoagulant protein C/protein S system in cord and adult plasma. Thromb Res. 2002 Mar 1;105(5):433-9. [PubMed:12062545]
  2. Hesselvik JF, Malm J, Dahlback B, Blomback M: Protein C, protein S and C4b-binding protein in severe infection and septic shock. Thromb Haemost. 1991 Feb 12;65(2):126-9. [PubMed:1828915]
  3. Cosio FG, Harker C, Batard MA, Brandt JT, Griffin JH: Plasma concentrations of the natural anticoagulants protein C and protein S in patients with proteinuria. J Lab Clin Med. 1985 Aug;106(2):218-22. [PubMed:3160800]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Ferroxidase activity
Specific Function
Ceruloplasmin is a blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iro...
Gene Name
CP
Uniprot ID
P00450
Uniprot Name
Ceruloplasmin
Molecular Weight
122204.45 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Thrombospondin receptor activity
Specific Function
Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostas...
Gene Name
F2
Uniprot ID
P00734
Uniprot Name
Prothrombin
Molecular Weight
70036.295 Da
References
  1. Omar MN, Shouk TA, Khaleq MA: Activity of blood coagulation and fibrinolysis during and after hydroxyethyl starch (HES) colloidal volume replacement. Clin Biochem. 1999 Jun;32(4):269-74. [PubMed:10463819]
  2. Cvirn G, Gallistl S, Koestenberger M, Kutschera J, Leschnik B, Muntean W: Alpha 2-macroglobulin enhances prothrombin activation and thrombin potential by inhibiting the anticoagulant protein C/protein S system in cord and adult plasma. Thromb Res. 2002 Mar 1;105(5):433-9. [PubMed:12062545]
  3. Gruber A, Cantwell AM, Di Cera E, Hanson SR: The thrombin mutant W215A/E217A shows safe and potent anticoagulant and antithrombotic effects in vivo. J Biol Chem. 2002 Aug 2;277(31):27581-4. Epub 2002 Jun 17. [PubMed:12070133]
  4. Conway EM, Van de Wouwer M, Pollefeyt S, Jurk K, Van Aken H, De Vriese A, Weitz JI, Weiler H, Hellings PW, Schaeffer P, Herbert JM, Collen D, Theilmeier G: The lectin-like domain of thrombomodulin confers protection from neutrophil-mediated tissue damage by suppressing adhesion molecule expression via nuclear factor kappaB and mitogen-activated protein kinase pathways. J Exp Med. 2002 Sep 2;196(5):565-77. [PubMed:12208873]
  5. Levi M, De Jonge E, van der Poll T: Recombinant human activated protein C (Xigris). Int J Clin Pract. 2002 Sep;56(7):542-5. [PubMed:12296618]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Heparin binding
Specific Function
Released during platelet aggregation. Neutralizes the anticoagulant effect of heparin because it binds more strongly to heparin than to the chondroitin-4-sulfate chains of the carrier molecule. Che...
Gene Name
PF4
Uniprot ID
P02776
Uniprot Name
Platelet factor 4
Molecular Weight
10844.78 Da
References
  1. Carr ME: Diabetes mellitus: a hypercoagulable state. J Diabetes Complications. 2001 Jan-Feb;15(1):44-54. [PubMed:11259926]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Serine-type endopeptidase inhibitor activity
Specific Function
Heparin-dependent serine protease inhibitor acting in body fluids and secretions. Inactivates serine proteases by binding irreversibly to their serine activation site. Involved in the regulation of...
Gene Name
SERPINA5
Uniprot ID
P05154
Uniprot Name
Plasma serine protease inhibitor
Molecular Weight
45674.315 Da
References
  1. Shen L, Villoutreix BO, Dahlback B: Involvement of Lys 62(217) and Lys 63(218) of human anticoagulant protein C in heparin stimulation of inhibition by the protein C inhibitor. Thromb Haemost. 1999 Jul;82(1):72-9. [PubMed:10456457]
  2. He X, Shen L, Bjartell A, Malm J, Lilja H, Dahlback B: The gene encoding vitamin K-dependent anticoagulant protein C is expressed in human male reproductive tissues. J Histochem Cytochem. 1995 Jun;43(6):563-70. [PubMed:7769227]
  3. Kobayashi H, Gabazza EC, Taguchi O, Wada H, Takeya H, Nishioka J, Yasui H, Kobayashi T, Hataji O, Suzuki K, Adachi Y: Protein C anticoagulant system in patients with interstitial lung disease. Am J Respir Crit Care Med. 1998 Jun;157(6 Pt 1):1850-4. [PubMed:9620917]
  4. Hayashi T, Suzuki K: [Molecular biology of protein C-thrombomodulin pathway. Structure and function, and basic studies on its clinical application]. Nihon Rinsho. 1993 Jun;51(6):1610-9. [PubMed:8391599]
  5. Berg DT, Gerlitz B, Shang J, Smith T, Santa P, Richardson MA, Kurz KD, Grinnell BW, Mace K, Jones BE: Engineering the proteolytic specificity of activated protein C improves its pharmacological properties. Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4423-8. Epub 2003 Apr 1. [PubMed:12671072]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Serine-type endopeptidase inhibitor activity
Specific Function
May be involved in the regulation of serine proteinases present in the brain or extravasated from the blood (By similarity). Inhibitor of cathepsin G, kallikrein-8 and thrombin. May play an importa...
Gene Name
SERPINB6
Uniprot ID
P35237
Uniprot Name
Serpin B6
Molecular Weight
42621.575 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Gamma-glutamyl carboxylase activity
Specific Function
Mediates the vitamin K-dependent carboxylation of glutamate residues to calcium-binding gamma-carboxyglutamate (Gla) residues with the concomitant conversion of the reduced hydroquinone form of vit...
Gene Name
GGCX
Uniprot ID
P38435
Uniprot Name
Vitamin K-dependent gamma-carboxylase
Molecular Weight
87560.065 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Receptor activity
Specific Function
Binds activated protein C. Enhances protein C activation by the thrombin-thrombomodulin complex; plays a role in the protein C pathway controlling blood coagulation.
Gene Name
PROCR
Uniprot ID
Q9UNN8
Uniprot Name
Endothelial protein C receptor
Molecular Weight
26671.245 Da
References
  1. Fukudome K, Ye X, Tsuneyoshi N, Tokunaga O, Sugawara K, Mizokami H, Kimoto M: Activation mechanism of anticoagulant protein C in large blood vessels involving the endothelial cell protein C receptor. J Exp Med. 1998 Apr 6;187(7):1029-35. [PubMed:9529319]
  2. Ruf W, Dorfleutner A, Riewald M: Specificity of coagulation factor signaling. J Thromb Haemost. 2003 Jul;1(7):1495-503. [PubMed:12871285]
  3. Castellino FJ, Liang Z, Volkir SP, Haalboom E, Martin JA, Sandoval-Cooper MJ, Rosen ED: Mice with a severe deficiency of the endothelial protein C receptor gene develop, survive, and reproduce normally, and do not present with enhanced arterial thrombosis after challenge. Thromb Haemost. 2002 Sep;88(3):462-72. [PubMed:12353077]
  4. Cerchiara E, Tirindelli MC, Giannetti B, Dicuonzo G, Avvisati G: [The numerous properties of the anticoagulant protein C]. Clin Ter. 2007 Mar-Apr;158(2):181-7. [PubMed:17566522]
  5. Liaw PC: Endogenous protein C activation in patients with severe sepsis. Crit Care Med. 2004 May;32(5 Suppl):S214-8. [PubMed:15118520]

Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23