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Identification
NameTirofiban
Accession NumberDB00775  (APRD00304)
TypeSmall Molecule
GroupsApproved
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
Synonyms
(2S)-2-(Butylsulfonylamino)-3-[4-(4-piperidin-4-ylbutoxy)phenyl]propanoic acid
N-(Butylsulfonyl)-O-(4-(4-piperidyl)butyl)-L-tyrosine
Tirofiban
Tirofibanum
External Identifiers
  • MK 383
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Aggrastatinjection, solution5 mg/100mLintravenousMedicure International Inc1998-05-14Not applicableUs
Aggrastatliquid0.25 mgintravenousCorrevio (Uk) Ltd1999-09-162013-02-06Canada
Aggrastatsolution5 mgintravenousCorrevio (Uk) Ltd2002-05-01Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
AggriblocAbbott
AgrastatMerck Sharp & Dohme
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Tirofiban hydrochloride
ThumbNot applicableDBSALT001454
Categories
UNIIGGX234SI5H
CAS number144494-65-5
WeightAverage: 440.597
Monoisotopic: 440.234492962
Chemical FormulaC22H36N2O5S
InChI KeyInChIKey=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
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
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as phenylpropanoic acids. These are compounds with a structure containing a benzene ring conjugated to a propanoic acid.
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassPhenylpropanoic acids
Sub ClassNot Available
Direct ParentPhenylpropanoic acids
Alternative Parents
Substituents
  • 3-phenylpropanoic-acid
  • Amphetamine or derivatives
  • Alpha-amino acid or derivatives
  • N-substituted-alpha-amino acid
  • Phenol ether
  • Amino fatty acid
  • Alkyl aryl ether
  • Fatty acyl
  • Benzenoid
  • Piperidine
  • Monocyclic benzene moiety
  • Aminosulfonyl compound
  • Sulfonyl
  • Sulfonic acid derivative
  • Sulfonamide
  • Azacycle
  • Organoheterocyclic compound
  • Secondary amine
  • Monocarboxylic acid or derivatives
  • Ether
  • Secondary aliphatic amine
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationFor treatment, in combination with heparin, of acute coronary syndrome, including patients who are to be managed medically and those undergoing PTCA or atherectomy.
PharmacodynamicsTirofiban 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 actionTirofiban 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.
Related Articles
AbsorptionNot Available
Volume of distribution
  • 22 to 42 L
Protein binding65%
Metabolism

Metabolism appears to be limited.

Route of eliminationIt 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 life2 hours
Clearance
  • 213 – 314 mL/min [Healthy subjects]
  • 152 – 267 mL/min [patients with coronary artery disease]
ToxicityNot Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Tirofiban Action PathwayDrug actionSMP00267
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9934
Blood Brain Barrier+0.5951
Caco-2 permeable-0.6716
P-glycoprotein substrateSubstrate0.8571
P-glycoprotein inhibitor INon-inhibitor0.5443
P-glycoprotein inhibitor IINon-inhibitor0.9898
Renal organic cation transporterNon-inhibitor0.8435
CYP450 2C9 substrateNon-substrate0.7483
CYP450 2D6 substrateNon-substrate0.7803
CYP450 3A4 substrateSubstrate0.5096
CYP450 1A2 substrateNon-inhibitor0.8569
CYP450 2C9 inhibitorNon-inhibitor0.8219
CYP450 2D6 inhibitorNon-inhibitor0.8967
CYP450 2C19 inhibitorNon-inhibitor0.7916
CYP450 3A4 inhibitorNon-inhibitor0.9023
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9498
Ames testNon AMES toxic0.7023
CarcinogenicityNon-carcinogens0.8449
BiodegradationNot ready biodegradable0.9525
Rat acute toxicity2.3684 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.5278
hERG inhibition (predictor II)Inhibitor0.7024
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Medicure international inc
Packagers
Dosage forms
FormRouteStrength
Injection, solutionintravenous5 mg/100mL
Liquidintravenous0.25 mg
Solutionintravenous5 mg
Prices
Unit descriptionCostUnit
Aggrastat 250 mcg/ml vial10.62USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2052073 No1998-05-262011-09-23Canada
CA2234364 No2000-02-082016-10-23Canada
US5658929 No1993-09-272010-09-27Us
US5733919 No1996-10-232016-10-23Us
US5965581 No1996-10-232016-10-23Us
US5972967 No1996-10-232016-10-23Us
US5978698 No1997-10-082017-10-08Us
US6136794 No1999-01-292019-01-29Us
US6770660 No2003-05-012023-05-01Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
water solubilityVery slightly solubleNot Available
logP1.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00317 mg/mLALOGPS
logP1.78ALOGPS
logP0.6ChemAxon
logS-5.1ALOGPS
pKa (Strongest Acidic)3.17ChemAxon
pKa (Strongest Basic)10.21ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area104.73 Å2ChemAxon
Rotatable Bond Count13ChemAxon
Refractivity117.48 m3·mol-1ChemAxon
Polarizability49.27 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

George Roby Thomas, Dawson James Reimer, Albert D. Friesen, “TRANSDERMAL PHARMACEUTICAL PREPARATION AND ADMINISTRATION OF TIROFIBAN.” U.S. Patent US20120029447, issued February 02, 2012.

US20120029447
General ReferencesNot Available
External Links
ATC CodesB01AC17
AHFS Codes
  • 20:12.18
PDB EntriesNot Available
FDA labelDownload (59.1 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AbciximabTirofiban may increase the anticoagulant activities of Abciximab.
AcenocoumarolTirofiban may increase the anticoagulant activities of Acenocoumarol.
Acetylsalicylic acidThe risk or severity of adverse effects can be increased when Tirofiban is combined with Acetylsalicylic acid.
AlteplaseTirofiban may increase the anticoagulant activities of Alteplase.
AnistreplaseTirofiban may increase the anticoagulant activities of Anistreplase.
ApixabanThe risk or severity of adverse effects can be increased when Tirofiban is combined with Apixaban.
Citric AcidTirofiban may increase the anticoagulant activities of Citric Acid.
CollagenaseThe risk or severity of adverse effects can be increased when Tirofiban is combined with Collagenase.
Dabigatran etexilateTirofiban may increase the anticoagulant activities of Dabigatran etexilate.
DalteparinTirofiban may increase the anticoagulant activities of Dalteparin.
DasatinibDasatinib may increase the anticoagulant activities of Tirofiban.
Deoxycholic AcidThe risk or severity of adverse effects can be increased when Tirofiban is combined with Deoxycholic Acid.
DicoumarolTirofiban may increase the anticoagulant activities of Dicoumarol.
Edetic AcidTirofiban may increase the anticoagulant activities of Edetic Acid.
EnoxaparinTirofiban may increase the anticoagulant activities of Enoxaparin.
Ethyl biscoumacetateTirofiban may increase the anticoagulant activities of Ethyl biscoumacetate.
Fondaparinux sodiumTirofiban may increase the anticoagulant activities of Fondaparinux sodium.
GlucosamineGlucosamine may increase the antiplatelet activities of Tirofiban.
HeparinTirofiban may increase the anticoagulant activities of Heparin.
Ibritumomab tiuxetanThe risk or severity of adverse effects can be increased when Tirofiban is combined with Ibritumomab.
IbrutinibThe risk or severity of adverse effects can be increased when Ibrutinib is combined with Tirofiban.
LimaprostLimaprost may increase the antiplatelet activities of Tirofiban.
ObinutuzumabThe risk or severity of adverse effects can be increased when Tirofiban is combined with Obinutuzumab.
Omega-3 fatty acidsOmega-3 fatty acids may increase the antiplatelet activities of Tirofiban.
Pentosan PolysulfateThe risk or severity of adverse effects can be increased when Pentosan Polysulfate is combined with Tirofiban.
PentoxifyllinePentoxifylline may increase the antiplatelet activities of Tirofiban.
PhenindioneTirofiban may increase the anticoagulant activities of Phenindione.
PhenprocoumonTirofiban may increase the anticoagulant activities of Phenprocoumon.
ReteplaseTirofiban may increase the anticoagulant activities of Reteplase.
RidogrelTirofiban may increase the anticoagulant activities of Ridogrel.
RivaroxabanTirofiban may increase the anticoagulant activities of Rivaroxaban.
StreptokinaseTirofiban may increase the anticoagulant activities of Streptokinase.
SulodexideTirofiban may increase the anticoagulant activities of Sulodexide.
TenecteplaseTirofiban may increase the anticoagulant activities of Tenecteplase.
TipranavirTipranavir may increase the antiplatelet activities of Tirofiban.
TositumomabThe risk or severity of adverse effects can be increased when Tirofiban is combined with Tositumomab.
TreprostinilTirofiban may increase the anticoagulant activities of Treprostinil.
UrokinaseTirofiban may increase the anticoagulant activities of Urokinase.
Vitamin EVitamin E may increase the antiplatelet activities of Tirofiban.
WarfarinTirofiban may increase the anticoagulant activities of Warfarin.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonist
General Function:
Metal ion binding
Specific Function:
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. ...
Gene Name:
ITGA2B
Uniprot ID:
P08514
Molecular Weight:
113375.96 Da
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:11076818 ]
  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:11342206 ]
  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:11565896 ]
  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:11929319 ]
  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:12057986 ]
  6. Juwana YB, Suryapranata H, Ottervanger JP, van 't Hof AW: Tirofiban for myocardial infarction. Expert Opin Pharmacother. 2010 Apr;11(5):861-6. doi: 10.1517/14656561003690005. [PubMed:20210689 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonist
General Function:
Virus receptor activity
Specific Function:
Integrin alpha-V/beta-3 (ITGAV:ITGB3) is a receptor for cytotactin, fibronectin, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin, vitronectin and von Willebrand factor. Integrin alpha-IIb/beta-3 (ITGA2B:ITGB3) is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. Integrins alpha-IIb/beta-3 and alpha-V/bet...
Gene Name:
ITGB3
Uniprot ID:
P05106
Molecular Weight:
87056.975 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  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:10592235 ]
  3. Juwana YB, Suryapranata H, Ottervanger JP, van 't Hof AW: Tirofiban for myocardial infarction. Expert Opin Pharmacother. 2010 Apr;11(5):861-6. doi: 10.1517/14656561003690005. [PubMed:20210689 ]
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Drug created on June 13, 2005 07:24 / Updated on May 26, 2016 02:09