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Identification
Name Tirofiban
Accession Number DB00775 (APRD00304)
Type small molecule
Groups approved
Description

Tirofiban prevents the blood from clotting during episodes of chest pain or a heart attack, or while the patient is undergoing a procedure to treat a blocked coronary artery. It is a non-peptide reversible antagonist of the platelet glycoprotein (GP) IIb/IIIa receptor, and inhibits platelet aggregation.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Synonyms Not Available
Salts Not Available
Brand names
Name Company
AGG
Aggrastat
Tirofiban [BAN:INN]
Brand mixtures Not Available
Categories
  • Platelet Aggregation Inhibitors
  • Fibrinolytic Agents
CAS number 144494-65-5
Weight Average: 440.597
Monoisotopic: 440.234492962
Chemical Formula C22H36N2O5S
InChI Key InChIKey=COKMIXFXJJXBQG-NRFANRHFSA-N
InChI
InChI=1S/C22H36N2O5S/c1-2-3-16-30(27,28)24-21(22(25)26)17-19-7-9-20(10-8-19)29-15-5-4-6-18-11-13-23-14-12-18/h7-10,18,21,23-24H,2-6,11-17H2,1H3,(H,25,26)/t21-/m0/s1
Plain Text
IUPAC Name
(2S)-2-(butane-1-sulfonamido)-3-{4-[4-(piperidin-4-yl)butoxy]phenyl}propanoic acid
SMILES
CCCCS(=O)(=O)N[C@@H](CC1=CC=C(OCCCCC2CCNCC2)C=C1)C(O)=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Phenethylamines
  • Amino Acids
  • Amphetamines
Substructures
  • Hydroxy Compounds
  • Acetates
  • Aliphatic and Aryl Amines
  • Phenols and Derivatives
  • Sulfonyls
  • Ethers
  • Benzene and Derivatives
  • Carboxylic Acids and Derivatives
  • Phenethylamines
  • Heterocyclic compounds
  • Aromatic compounds
  • Anisoles
  • Sulfonamides
  • Amino Acids
  • Phenyl Esters
  • Amphetamines
  • Piperidines
Pharmacology
Indication For treatment, in combination with heparin, of acute coronary syndrome, including patients who are to be managed medically and those undergoing PTCA or atherectomy.
Pharmacodynamics Tirofiban prevents the blood from clotting during episodes of chest pain or a heart attack, or while the patient is undergoing a procedure to treat a blocked coronary artery. It is a non-peptide antagonist of the platelet glycoprotein (GP) IIb/IIIa receptor, and inhibits platelet aggregation. When administered intravenously, tirofiban inhibits ex vivo platelet aggregation in a dose- and concentration-dependent manner. When given according to the recommended regimen, >90% inhibition is attained by the end of the 30-minute infusion. Tirofiban has been recently shown in patients with unstable angina to reduce ischemic events at 48 hours following infusion when compared to standard heparin therapy.
Mechanism of action Tirofiban is a reversible antagonist of fibrinogen binding to the GP IIb/IIIa receptor, the major platelet surface receptor involved in platelet aggregation. Platelet aggregation inhibition is reversible following cessation of the infusion of tirofiban.
Absorption Not Available
Volume of distribution
  • 22 to 42 L
Protein binding 65%
Metabolism Metabolism appears to be limited.
Route of elimination It is cleared from the plasma largely by renal excretion, with about 65% of an administered dose appearing in urine and about 25% in feces, both largely as unchanged tirofiban.
Half life 2 hours
Clearance
  • 213 – 314 mL/min [Healthy subjects]
  • 152 – 267 mL/min [patients with coronary artery disease]
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00267 Tirofiban Pathway SMP00267
Pharmacoeconomics
Manufacturers
  • Medicure international inc
Packagers
Dosage forms
Form Route Strength
Solution Intravenous
Prices
Unit description Cost Unit
Aggrastat 250 mcg/ml vial 10.62 USD ml
Patents
Country Patent Number Approved Expires (estimated)
United States 6136794 1999-01-29 2019-01-29
United States 5658929 1993-09-27 2010-09-27
Canada 2234364 2000-02-08 2016-10-23
Canada 2052073 1998-05-26 2011-09-23
Properties
State solid
Melting point Not Available
Experimental Properties
Property Value Source
water solubility Very slightly soluble PhysProp
logP 1.4 PhysProp
Predicted Properties
Property Value Source
water solubility 3.17e-03 g/l ALOGPS
logP 1.78 ALOGPS
logP 0.6 ChemAxon Molconvert
logS -5.1 ALOGPS
pKa 10.89 ChemAxon Molconvert
hydrogen acceptor count 6 ChemAxon Molconvert
hydrogen donor count 3 ChemAxon Molconvert
polar surface area 104.73 ChemAxon Molconvert
rotatable bond count 13 ChemAxon Molconvert
refractivity 117.48 ChemAxon Molconvert
polarizability 49.27 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Compound C07965 Link_out
PubChem Compound 60947 Link_out
PubChem Substance 46504678 Link_out
ChemSpider 54912 Link_out
ChEBI 9605 Link_out
ChEMBL 9605 Link_out
Therapeutic Targets Database DAP000696 Link_out
PharmGKB PA451698 Link_out
HET AGG Link_out
Drug Product Database 2240706 Link_out
RxList http://www.rxlist.com/cgi/generic/tiro.htm Link_out
Drugs.com http://www.drugs.com/cdi/tirofiban.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Tirofiban Link_out
ATC Codes
  • B01AC17
AHFS Codes
  • 20:12.18
PDB Entries Not Available
FDA label show (59.1 KB)
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Abciximab Additive effects. Concomitant use is contraindicated.
Eptifibatide Additive effects. Concomitant use is contraindicated.
Ginkgo biloba Additive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.
Treprostinil The prostacyclin analogue, Treprostinil, increases the risk of bleeding when combined with the antiplatelet agent, Tirofiban. Monitor for increased bleeding during concomitant thearpy.
Food Interactions Not Available
Targets

1. Integrin alpha-IIb

Pharmacological action: yes
Actions: antagonist

Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognizes the sequence H-H-L-G-G-G-A-K-Q-A-G-D-V in fibrinogen gamma chain. Following activation integrin alpha- IIb/beta-3 brings about platelet/platelet interaction through binding of soluble fibrinogen. This step leads to rapid platelet aggregation which physically plugs ruptured endothelial cell surface

Organism class: human
UniProt ID: P08514 Link_out
Gene: ITGA2B Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Theroux P, Alexander J Jr, Pharand C, Barr E, Snapinn S, Ghannam AF, Sax FL: Glycoprotein IIb/IIIa receptor blockade improves outcomes in diabetic patients presenting with unstable angina/non-ST-elevation myocardial infarction: results from the Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) study. Circulation. 2000 Nov 14;102(20):2466-72. Pubmed
  2. Dickfeld T, Ruf A, Pogatsa-Murray G, Muller I, Engelmann B, Taubitz W, Fischer J, Meier O, Gawaz M: Differential antiplatelet effects of various glycoprotein IIb-IIIa antagonists. Thromb Res. 2001 Jan 15;101(2):53-64. Pubmed
  3. von Segesser LK, Mueller X, Marty B, Horisberger J, Corno A: Alternatives to unfractionated heparin for anticoagulation in cardiopulmonary bypass. Perfusion. 2001 Sep;16(5):411-6. Pubmed
  4. Kondo K, Umemura K: Clinical pharmacokinetics of tirofiban, a nonpeptide glycoprotein IIb/IIIa receptor antagonist: comparison with the monoclonal antibody abciximab. Clin Pharmacokinet. 2002;41(3):187-95. Pubmed
  5. Roffi M, Moliterno DJ, Meier B, Powers ER, Grines CL, DiBattiste PM, Herrmann HC, Bertrand M, Harris KE, Demopoulos LA, Topol EJ: Impact of different platelet glycoprotein IIb/IIIa receptor inhibitors among diabetic patients undergoing percutaneous coronary intervention: : Do Tirofiban and ReoPro Give Similar Efficacy Outcomes Trial (TARGET) 1-year follow-up. Circulation. 2002 Jun 11;105(23):2730-6. Pubmed
  6. Juwana YB, Suryapranata H, Ottervanger JP, van ’t Hof AW: Tirofiban for myocardial infarction. Expert Opin Pharmacother. 2010 Apr;11(5):861-6. Pubmed

2. Integrin beta-3

Pharmacological action: yes
Actions: antagonist

Integrin alpha-V/beta-3 is a receptor for cytotactin, fibronectin, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin, vitronectin and von Willebrand factor. Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. Integrins alpha-IIb/beta-3 and alpha-V/beta-3 recognize the sequence R-G-D in a wide array of ligands. Integrin alpha-IIb/beta-3 recognizes the sequence H-H-L-G-G-G-A-K-Q-A-G-D-V in fibrinogen gamma chain. Following activation integrin alpha- IIb/beta-3 brings about platelet/platelet interaction through binding of soluble fibrinogen. This step leads to rapid platelet aggregation which physically plugs ruptured endothelial surface. In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions

Organism class: human
UniProt ID: P05106 Link_out
Gene: ITGB3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed
  3. Juwana YB, Suryapranata H, Ottervanger JP, van ’t Hof AW: Tirofiban for myocardial infarction. Expert Opin Pharmacother. 2010 Apr;11(5):861-6. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 14, 2012 11:43