Desmoteplase

Identification

Name
Desmoteplase
Accession Number
DB04925
Type
Biotech
Groups
Investigational
Biologic Classification
Protein Based Therapies
Other protein based therapies
Description

Desmoteplase is a chemical in the saliva of vampire bats. It activates plasminogen to the serine protease, plasmin. Plasmin acts by breaking down fibrin blood clots. When a vampire bat bites its victim, it secretes an enzyme that prevents the blood from clotting. The enzyme is called DSPA (Desmodus rotundus salivary plasminogen activator) and scientists are using DSPA as stroke and heart attack medication. Desmoteplase is a recombinant form of vampire bat DSPA (Salivary plasminogen activator alpha 1).

Protein chemical formula
Not Available
Protein average weight
Not Available
Sequences
>P98119|URT1_DESRO Salivary plasminogen activator alpha 1 precursor - Desmodus rotundus
MVNTMKTKLLCVLLLCGAVFSLPRQETYRQLARGSRAYGVACKDEITQMTYRRQESWLRP
EVRSKRVEHCQCDRGQARCHTVPVNSCSEPRCFNGGTCWQAVYFSDFVCQCPAGYTGKRC
EVDTRATCYEGQGVTYRGTWSTAESRVECINWNSSLLTRRTYNGRMPDAFNLGLGNHNYC
RNPNGAPKPWCYVIKAGKFTSESCSVPVCSKATCGLRKYKEPQLHSTGGLFTDITSHPWQ
AAIFAQNRRSSGERFLCGGILISSCWVLTAAHCFQESYLPDQLKVVLGRTYRVKPGEEEQ
TFKVKKYIVHKEFDDDTYNNDIALLQLKSDSPQCAQESDSVRAICLPEANLQLPDWTECE
LSGYGKHKSSSPFYSEQLKEGHVRLYPSSRCAPKFLFNKTVTNNMLCAGDTRSGEIYPNV
HDACQGDSGGPLVCMNDNHMTLLGIISWGVGCGEKDVPGVYTKVTNYLGWIRDNMHL
Download FASTA Format
Synonyms
  • Desmodus rotundus salivary plasminogen activator
  • DSPA
Categories
UNII
T36L245S3T
CAS number
145137-38-8

Pharmacology

Indication

Investigated for use/treatment in cerebral ischemia and strokes.

Pharmacodynamics

Desmoteplase is a novel thrombolytic agent derived from vampire-bat saliva. It is genetically related to the clot buster tissue plasminogen activator (t-PA) but is more potent and demonstrates a safer toxicity profile (desmoteplase does not promote kainate- or NMDA-mediated neurotoxicity in vivo). Plasminogen activators are enzymes found in all vertebrate species investigated so far. Their physiological function is the generation of localized proteolysis in the context of tissue remodeling, wound healing and neuronal plasticity.

Mechanism of action

Desmoteplase targets and destroys fibrin, the structural scaffold of blood clots.

TargetActionsOrganism
UPlasminogenNot AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(1,2,6,7-3H)TestosteroneThe therapeutic efficacy of Desmoteplase can be increased when used in combination with (1,2,6,7-3H)Testosterone.
(R)-warfarinThe risk or severity of bleeding can be increased when Desmoteplase is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding can be increased when Desmoteplase is combined with (S)-Warfarin.
1-TestosteroneThe therapeutic efficacy of Desmoteplase can be increased when used in combination with 1-Testosterone.
18-methyl-19-nortestosteroneThe therapeutic efficacy of Desmoteplase can be increased when used in combination with 18-methyl-19-nortestosterone.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when Desmoteplase is combined with 4-hydroxycoumarin.
4-HydroxytestosteroneThe therapeutic efficacy of Desmoteplase can be increased when used in combination with 4-Hydroxytestosterone.
5beta-dihydrotestosteroneThe therapeutic efficacy of Desmoteplase can be increased when used in combination with 5beta-dihydrotestosterone.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Desmoteplase.
AceclofenacThe risk or severity of bleeding and hemorrhage can be increased when Aceclofenac is combined with Desmoteplase.
Food Interactions
Not Available

References

General References
  1. Grandjean C, McMullen PC, Newschwander G: Vampire bats yield potent clot buster for ischemic stroke. J Cardiovasc Nurs. 2004 Nov-Dec;19(6):417-20. [PubMed:15529064]
  2. Hacke W, Albers G, Al-Rawi Y, Bogousslavsky J, Davalos A, Eliasziw M, Fischer M, Furlan A, Kaste M, Lees KR, Soehngen M, Warach S: The Desmoteplase in Acute Ischemic Stroke Trial (DIAS): a phase II MRI-based 9-hour window acute stroke thrombolysis trial with intravenous desmoteplase. Stroke. 2005 Jan;36(1):66-73. Epub 2004 Nov 29. [PubMed:15569863]
  3. Schleuning WD: Vampire bat plasminogen activator DSPA-alpha-1 (desmoteplase): a thrombolytic drug optimized by natural selection. Haemostasis. 2001 May-Dec;31(3-6):118-22. [PubMed:11910176]
  4. Liberatore GT, Samson A, Bladin C, Schleuning WD, Medcalf RL: Vampire bat salivary plasminogen activator (desmoteplase): a unique fibrinolytic enzyme that does not promote neurodegeneration. Stroke. 2003 Feb;34(2):537-43. [PubMed:12574572]
  5. Reddrop C, Moldrich RX, Beart PM, Farso M, Liberatore GT, Howells DW, Petersen KU, Schleuning WD, Medcalf RL: Vampire bat salivary plasminogen activator (desmoteplase) inhibits tissue-type plasminogen activator-induced potentiation of excitotoxic injury. Stroke. 2005 Jun;36(6):1241-6. Epub 2005 May 5. [PubMed:15879331]
  6. Hoffmann JJ, Kops O: Inhibition of desmoteplase-induced fibrinolytic activity in vitro. J Thromb Thrombolysis. 2005 Aug;20(1):23-6. [PubMed:16133891]
  7. Furlan AJ, Eyding D, Albers GW, Al-Rawi Y, Lees KR, Rowley HA, Sachara C, Soehngen M, Warach S, Hacke W: Dose Escalation of Desmoteplase for Acute Ischemic Stroke (DEDAS): evidence of safety and efficacy 3 to 9 hours after stroke onset. Stroke. 2006 May;37(5):1227-31. Epub 2006 Mar 30. [PubMed:16574922]
External Links
UniProt
P98119
PubChem Substance
347909849
Wikipedia
Desmoteplase

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1, 2CompletedTreatmentStrokes1
2CompletedTreatmentAcute Ischemic Stroke (AIS)1
2CompletedTreatmentStrokes1
3CompletedTreatmentStroke, Acute1
3CompletedTreatmentStrokes1
3TerminatedTreatmentStrokes1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
Not 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
Unknown
General Function
Serine-type peptidase activity
Specific Function
Plasmin dissolves the fibrin of blood clots and acts as a proteolytic factor in a variety of other processes including embryonic development, tissue remodeling, tumor invasion, and inflammation. In...
Gene Name
PLG
Uniprot ID
P00747
Uniprot Name
Plasminogen
Molecular Weight
90568.415 Da
References
  1. Dafer RM, Biller J: Desmoteplase in the treatment of acute ischemic stroke. Expert Rev Neurother. 2007 Apr;7(4):333-7. [PubMed:17425487]

Drug created on October 21, 2007 16:23 / Updated on November 02, 2018 06:07