TIROFIBAN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C22H36N2O5S
Molecular Weight	440.597
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCCCS(=O)(=O)N[C@@H](CC1=CC=C(OCCCCC2CCNCC2)C=C1)C(O)=O

InChI

InChIKey=COKMIXFXJJXBQG-NRFANRHFSA-N

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

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/1998/20912lbl.pdf
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/19343166 | https://www.ncbi.nlm.nih.gov/pubmed/9878994

Tirofiban is a non-peptide antagonist of the platelet glycoprotein (GP) IIb/IIIa receptor. Tirofiban is a reversible, competitive inhibitor of GP IIb/IIIa receptors, exerting its effects via the prevention of the binding of fibrinogen and other ligands, resulting in the inhibition of the last common step of thrombi formation. Tirofiban was discovered by Merck, USA, and was approved by the FDA in 1998 under the trade name AGGRASTAT. AGGRASTAT, in combination with heparin, is indicated for the treatment of acute coronary syndrome, including patients who are to be managed medically and those undergoing percutaneous transluminal coronary angioplasty or atherectomy. AGGRASTAT reduces the risk of ischaemic complications in patients with unstable angina/non-Q-wave myocardial infarction and high-risk patients undergoing revascularisation when used against a background of heparin and aspirin. Furthermore, the drug has an acceptable tolerability profile. Therefore, intravenous tirofiban is likely to be used as an adjunct to heparin and aspirin in patients with acute coronary syndromes including high-risk patients undergoing revascularisation.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Integrin alpha-IIb/beta-3 14 Target ID: CHEMBL2093869 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19343166	Antagonist 2778		15.0 nM [Kd]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Acute coronary syndrome 33 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/1998/20912lbl.pdf	Primary		Approved 8429	AGGRASTAT Approved Use AGGRASTAT, in combination with heparin, is indicated for the treatment of acute coronary syndrome, including patients who are to be managed medically and those undergoing percutaneous transluminal coronary angioplasty or atherectomy. In this setting, AGGRASTAT has been shown to decrease the rate of a combined endpoint of death, new myocardial infarction or refractory ischemia/repeat cardiac procedure. Launch Date 1998

AUC

Value	Dose	Analyte	Population
193.4 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7955799/	0.15 μg/kg/min other, intravenous dose: 0.15 μg/kg/min route of administration: Intravenous experiment type: OTHER co-administered:	TIROFIBAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
209.5 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7955799/	0.2 μg/kg/min other, intravenous dose: 0.2 μg/kg/min route of administration: Intravenous experiment type: OTHER co-administered:	TIROFIBAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
92.5 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7955799/	0.1 μg/kg/min other, intravenous dose: 0.1 μg/kg/min route of administration: Intravenous experiment type: OTHER co-administered:	TIROFIBAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
1.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7955799/	0.15 μg/kg/min other, intravenous dose: 0.15 μg/kg/min route of administration: Intravenous experiment type: OTHER co-administered:	TIROFIBAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7955799/	0.2 μg/kg/min other, intravenous dose: 0.2 μg/kg/min route of administration: Intravenous experiment type: OTHER co-administered:	TIROFIBAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7955799/	0.1 μg/kg/min other, intravenous dose: 0.1 μg/kg/min route of administration: Intravenous experiment type: OTHER co-administered:	TIROFIBAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737	substrate 1037	substrate 1217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP2C19 991 CYP1A2 1054

Drug as victim

Target	Modality	Activity
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10534322/ Page: -	no
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10534322/ Page: -	no
CYP2C19 991	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10534322/ Page: -	yes
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10534322/ Page: -	yes
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10534322/ Page: -	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:9605	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:9605
ChemicalBook	CB9169083	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB9169083
MolPort	MolPort-006-167-632	https://www.molport.com/shop/molecule-link/MolPort-006-167-632
ZINC	ZINC000003806104	http://zinc15.docking.org/substances/ZINC000003806104
eMolecules	6843975	https://www.emolecules.com/cgi-bin/more?vid=6843975

PubMed

Title	Date	PubMed
Platelet aggregation inhibition with glycoprotein IIb--IIIa inhibitors.	2001 Apr	11406724
[GPIIb-IIIa inhibitors].	2001 Apr	11386043
Safety and efficacy of thrombolysis with alteplase (50 mg) plus tirofiban versus alteplase (100 mg) alone in acute myocardial infarction: preliminary findings.	2001 Aug	11577835
Platelet glycoprotein IIb/IIIa-receptor inhibitors in patients with acute coronary syndromes or undergoing percutaneous coronary interventions: a review.	2001 Aug	11558855
Estimation of anti-platelet drugs on human platelet aggregation with a novel whole blood aggregometer by a screen filtration pressure method.	2001 Aug	11498527
The A-to-Z Trial: Methods and rationale for a single trial investigating combined use of low-molecular-weight heparin with the glycoprotein IIb/IIIa inhibitor tirofiban and defining the efficacy of early aggressive simvastatin therapy.	2001 Aug	11479456
Comparative efficacy of fibrinogen and platelet supplementation on the in vitro reversibility of competitive glycoprotein IIb/IIIa (alphaIIb/beta3) receptor-directed platelet inhibition.	2001 Aug	11479455
GP IIb/IIIa inhibitors in coronary artery disease management: what the latest trials tell us.	2001 Dec	11765119
A risk stratification scheme for selection of a glycoprotein IIb/IIIa inhibitor during percutaneous coronary intervention based on clinical and angiographic criteria.	2001 Dec 1	11728356
Glycoprotein IIb/IIIa receptor blockers in acute coronary syndromes.	2001 Dec 8	11747950
TACTICS-TIMI 18 shows positive results of invasive approach.	2001 Feb-Mar	11474693
[Inhibitors of platelet glycoprotein IIb-IIIa in cardiology].	2001 Jan-Feb	11419288
Anti-GPIIb/IIIa drugs: current strategies and future directions.	2001 Jul	11487034
Use of ICHOR-platelet works to assess platelet function in patients treated with GP IIb/IIIa inhibitors.	2001 Jul	11458412
Glycoprotein IIb/IIIa inhibitors: more different than alike?	2001 Jul	11458404
Diffuse alveolar hemorrhage after clopidogrel use.	2001 Jul	11435642
Stability and compatibility of tirofiban hydrochloride during simulated Y-site administration with other drugs.	2001 Jul 1	11449879
Eptifibatide and 7E3, but not tirofiban, inhibit alpha(v)beta(3) integrin-mediated binding of smooth muscle cells to thrombospondin and prothrombin.	2001 Jul 31	11479257
Randomized comparison of ticlopidine and clopidogrel after intracoronary stent implantation in a broad patient population.	2001 Jul 31	11479250
Deep venous thrombosis prophylaxis is not indicated for laparoscopic cholecystectomy.	2001 Jul-Sep	11548825
Optimal treatment of acute coronary syndromes--an evolving strategy.	2001 Jun 21	11419433
Future trials of antiplatelet agents in cardiac ischemia.	2001 Jun 21	11419432
Comparison of two platelet glycoprotein IIb/IIIa inhibitors, tirofiban and abciximab, for the prevention of ischemic events with percutaneous coronary revascularization.	2001 Jun 21	11419425
Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban.	2001 Jun 21	11419424
[Lysis of an extensive thrombus in the internal carotid artery using a glycoprotein IIb/IIIa receptor antagonist].	2001 Jun 8	11441664
Augmentation of in-vitro clot dissolution by low frequency high-intensity ultrasound combined with antiplatelet and antithrombotic drugs.	2001 May	11577261
Elevation in serum troponin I predicts the benefit of tirofiban.	2001 May	11577259
Short-term comparative outcomes associated with the use of GP IIb/IIIa antagonists in patients undergoing coronary intervention.	2001 May	11577258
Glycoprotein IIb/IIIa antagonists and low-molecular weight heparin in acute coronary syndromes.	2001 May	11407108
Exit of platelet glycoprotein-IIb/IIIa-receptor inhibitors?	2001 May 12	11386297
Point-of-care measured platelet inhibition correlates with a reduced risk of an adverse cardiac event after percutaneous coronary intervention: results of the GOLD (AU-Assessing Ultegra) multicenter study.	2001 May 29	11382726
Monitoring platelet function in glycoprotein IIB/IIIA inhibitor therapy.	2001 May 29	11382717
Small peptide GP IIb/IIIa receptor inhibitors as upstream therapy in non-ST-segment elevation acute coronary syndromes: results of the PURSUIT, PRISM, PRISM-PLUS, TACTICS, and PARAGON trials.	2001 Nov	11704707
ESPRIT in context: pharmacology matters!	2001 Nov	11603901
[Comparison of 2 platelet glycoprotein IIb/IIIa inhibitors, tirofiban and abciximab, for the prevention of ischemic events with percutaneous coronary revascularization].	2001 Oct	11723620
Increased reperfusion by glycoprotein IIb/IIIa receptor antagonist administration in case of unsuccessful and failed thrombolysis in patients with acute myocardial infarction: a pilot study.	2001 Oct	11721719
Resolution of a spontaneous coronary artery thrombus with a new antiplatelet agent.	2001 Sep	11573060
Alternatives to unfractionated heparin for anticoagulation in cardiopulmonary bypass.	2001 Sep	11565896
Pharmacodynamic characterization of the interaction between abciximab or tirofiban with unfractionated or a low molecular weight heparin in healthy subjects.	2001 Sep	11560562
Tirofiban therapy does not increase the risk of hemorrhage after emergency coronary surgery.	2001 Sep	11547328
Adjunctive therapies in the cath lab. Use of combination glycoprotein IIb/IIIa inhibitor and direct thrombin inhibitor drugs to support percutaneous coronary stent placement in a patient with renal insufficiency and heparin-induced thrombocytopenia.	2001 Sep	11533507
Adjunctive therapies in the cath lab. Intracoronary tirofiban infusion in a case with massive intracoronary thrombus.	2001 Sep	11533506
Adjunctive therapies in the cath lab. Combination of tirofiban and alteplase in acute myocardial infarction.	2001 Sep	11533504
Platelet glycoprotein inhibitors in patients with medically managed acute coronary syndrome: does the enthusiasm exceed the science?	2001 Sep	11524643
A risk score system for predicting adverse outcomes and magnitude of benefit with glycoprotein IIb/IIIa inhibitor therapy in patients with unstable angina pectoris.	2001 Sep 1	11524055
Differential inhibition of adenosine diphosphate- versus thrombin receptor-activating peptide-stimulated platelet fibrinogen binding by abciximab due to different glycoprotein IIb/IIIa activation kinetics.	2001 Sep 1	11520817
Dissociation of glycoprotein IIb/IIIa antagonists from platelets does not result in fibrinogen binding or platelet aggregation.	2001 Sep 18	11560852
Oral glycoprotein IIb/IIa antagonists for unstable angina--is there still a chance for the oral substances?	2001 Sep 30	11567679
The role of glycoprotein IIb/IIIa inhibition in the management of acute coronary syndromes.	2001 Sep-Oct	11604974
Cost effectiveness of invasive strategy in unstable coronary disease--what are we waiting for?	2002 Jan	11741352

Patents

Sample Use Guides

In Vivo Use Guide

In most patients, AGGRASTAT should be administered intravenously, at an initial rate of 0.4 µg/kg/min for 30 minutes and then continued at 0.1 µg/kg/min. Patients with severe renal insufficiency (creatinine clearance <30 mL/min) should receive half the usual rate of infusion.

Route of Administration: Intravenous

In Vitro Use Guide

Platelet-rich plasma from each subject was incubated in vitro with increasing concentrations of tirofiban (25, 37.5, and 50ng/ml), patients with moderate to severe renal dysfunction suppress their platelet aggregation to <10% with 25ng/ml of tirofiban, one-third of the standard effective dose for patients with normal renal function.

Name

Type

Language

TIROFIBAN

Official Name

English

TIROFIBAN [MI]

Common Name

English

TIROFIBAN [VANDF]

Common Name

English

AGRASTAT

Brand Name

English

TIROFIBAN [HSDB]

Common Name

English

tirofiban [INN]

Common Name

English

Tirofiban [WHO-DD]

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000008832