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 2849		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 8583	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
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
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

T_1/2

Value	Dose	Analyte	Population
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
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

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946	substrate 1193	substrate 1388

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP2C19 1119 CYP1A2 1197

Drug as victim

Target	Modality	Activity
CYP1A2 1197	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/10534322/ Page: -	no
CYP2C9 1193	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/10534322/ Page: -	no
CYP2C19 1119	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/10534322/ Page: -	yes
CYP2D6 1388	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/10534322/ Page: -	yes
CYP3A4 1946	substrate 4014 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
eMolecules	6843975	https://www.emolecules.com/cgi-bin/more?vid=6843975
MolPort	MolPort-006-167-632	https://www.molport.com/shop/molecule-link/MolPort-006-167-632
ZINC	ZINC000003806104	http://zinc15.docking.org/substances/ZINC000003806104

PubMed

Title	Date	PubMed
Bleeding risk of tirofiban, a nonpeptide GPIIb/IIIa platelet receptor antagonist in progressive stroke: an open pilot study.	2001	11721100
[GPIIb-IIIa inhibitors].	2001 Apr	11386043
[Pathophysiology of platelet activation and pharmacology of GPIIb/IIIa inhibitors].	2001 Apr	11349624
Antiplatelet effects of abciximab, tirofiban and eptifibatide in patients undergoing coronary stenting.	2001 Apr	11300442
A comparative study of light transmission aggregometry and automated bedside platelet function assays in patients undergoing percutaneous coronary intervention and receiving abciximab, eptifibatide, or tirofiban.	2001 Apr	11285593
Inhibition of tissue factor-activated platelets by low-molecular-weight heparins and glycoprotein IIb/IIIa receptor antagonist.	2001 Apr 15	11323025
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
Estimation of anti-platelet drugs on human platelet aggregation with a novel whole blood aggregometer by a screen filtration pressure method.	2001 Aug	11498527
Perioperative use of tirofiban hydrochloride (Aggrastat) does not increase surgical bleeding after emergency or urgent coronary artery bypass grafting.	2001 Dec	11726894
Treatment of acute basilar artery thrombosis with a combination of systemic alteplase and tirofiban, a nonpeptide platelet glycoprotein IIb/IIIa inhibitor: report of four cases.	2001 Dec	11719681
Standardized ultrasound as a new method to induce platelet aggregation: evaluation, influence of lipoproteins and of glycoprotein IIb/IIIa antagonist tirofiban.	2001 Dec	11704433
Anticoagulation during cardiopulmonary bypass in patients with heparin-induced thrombocytopenia type II and renal impairment using heparin and the platelet glycoprotein IIb-IIIa antagonist tirofiban.	2001 Feb	11176088
Upstream use of tirofiban in patients admitted for an acute coronary syndrome in hospitals with or without facilities for invasive management. PRISM-PLUS Investigators.	2001 Feb 15	11179517
[Update on the treatment with platelet antiaggregation agents].	2001 Jan	11291339
Complicated acute myocardial infarction.	2001 Jan	11165841
Differential antiplatelet effects of various glycoprotein IIb-IIIa antagonists.	2001 Jan 15	11342206
[Tirofiban (Aggrastat). A non-peptide glycoprotein IIb/IIIa receptor inhibitor].	2001 Jan 22	11218789
Diffuse alveolar hemorrhage after clopidogrel use.	2001 Jul	11435642
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
[Acute coronary syndromes: an update. I. Pathogenesis and drug therapy].	2001 Mar	11349620
Unexpected flow cytometric results with two small GPIIb/IIIa blockers: eptifibatide and tirofiban.	2001 Mar	11307832
Effect of Ca2+ chelation on the platelet inhibitory ability of the GPIIb/IIIa antagonists abciximab, eptifibatide and tirofiban.	2001 Mar	11307828
Platelet glycoprotein IIb/IIIa receptor antagonists and coronary artery disease.	2001 Mar	11177658
Meta-analysis of effectiveness and safety of abciximab versus eptifibatide or tirofiban in percutaneous coronary intervention.	2001 Mar 1	11230835
Elevation in serum troponin I predicts the benefit of tirofiban.	2001 May	11577259
Glycoprotein IIb/IIIa antagonists and low-molecular weight heparin in acute coronary syndromes.	2001 May	11407108
Quantification by flow cytometry of the efficacy of and interindividual variation of platelet inhibition induced by treatment with tirofiban and abciximab.	2001 May	11352081
Exit of platelet glycoprotein-IIb/IIIa-receptor inhibitors?	2001 May 12	11386297
Effects on thrombin generation of the platelet glycoprotein IIb/IIIa inhibitors abciximab versus tirofiban during coronary intervention.	2001 May 15	11356410
[Indications for intravenous GPIIb/IIIa receptor inhibitors in acute coronary syndrome without prolonged ST syndrome].	2001 Nov	11794966
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
Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes.	2001 Nov 22	11794229
Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes.	2001 Nov 22	11794228
Acute coronary syndrome without ST elevation: implementation of new guidelines.	2001 Nov 3	11705583
Intravenous glycoprotein IIb/IIIa inhibition in non-ST segment elevation acute coronary syndromes.	2001 Nov-Dec	11727277
[Comparison of 2 platelet glycoprotein IIb/IIIa inhibitors, tirofiban and abciximab, for the prevention of ischemic events with percutaneous coronary revascularization].	2001 Oct	11723620
[Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban].	2001 Oct	11723619
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
Use of coronary revascularization in patients with unstable and non-ST-segment elevation acute myocardial infarction.	2001 Oct 18	11694216
Interpreting new treatment guidelines for non-ST-segment elevation acute coronary syndromes.	2001 Oct 18	11694215
Should patients with unstable coronary syndromes routinely undergo cardiac catheterization and appropriate revascularization?	2001 Sep	11674901
Pharmacodynamic characterization of the interaction between abciximab or tirofiban with unfractionated or a low molecular weight heparin in healthy subjects.	2001 Sep	11560562
Adjunctive therapies in the cath lab. Combination of tirofiban and alteplase in acute myocardial infarction.	2001 Sep	11533504
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

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

AGRASTAT

Preferred Name

English

TIROFIBAN [MI]

Common Name

English

TIROFIBAN [VANDF]

Common 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