TIROFIBAN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C22H36N2O5S
Molecular Weight	440.5986
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])(Cc1ccc(cc1)OCCCCC2CCNCC2)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 13 Target ID: CHEMBL2093869 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19343166	Antagonist 2575		15.0 nM [Kd]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Acute coronary syndrome 27 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/1998/20912lbl.pdf	Primary		Approved 8043	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 8.9510399E11

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 1601	substrate 936	substrate 1118

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP2C19 910 CYP1A2 972

Drug as victim

Target	Modality	Activity
CYP1A2 972	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/10534322/ Page: -	no
CYP2C9 936	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/10534322/ Page: -	no
CYP2C19 910	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/10534322/ Page: -	yes
CYP2D6 1118	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/10534322/ Page: -	yes
CYP3A4 1601	substrate 3113 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
Bleeding risk of tirofiban, a nonpeptide GPIIb/IIIa platelet receptor antagonist in progressive stroke: an open pilot study.	2001	11721100
Platelet aggregation inhibition with glycoprotein IIb--IIIa inhibitors.	2001 Apr	11406724
[GPIIb-IIIa inhibitors].	2001 Apr	11386043
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
GP IIb/IIIa inhibitors in coronary artery disease management: what the latest trials tell us.	2001 Dec	11765119
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
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
Platelet inhibition after glycoprotein IIb/IIIa inhibitor therapy.	2001 Dec 18	11748127
TACTICS-TIMI 18 shows positive results of invasive approach.	2001 Feb-Mar	11474693
Complicated acute myocardial infarction.	2001 Jan	11165841
[Update on tirofiban].	2001 Jan 20	11244822
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
Optimal treatment of acute coronary syndromes--an evolving strategy.	2001 Jun 21	11419433
[Lysis of an extensive thrombus in the internal carotid artery using a glycoprotein IIb/IIIa receptor antagonist].	2001 Jun 8	11441664
Initial experience with a newer generation coronary stent.	2001 Mar	11231647
Administration of abciximab to patients receiving tirofiban or eptifibatide: effect on platelet function.	2001 Mar 1	11693761
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
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
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
[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
ESPRIT in context: pharmacology matters!	2001 Nov	11603901
[Rescue thrombectomy after stent implantation in a degenerating aortocoronary bypass].	2001 Nov 15	11760656
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 GP IIB/IIIA inhibitors and their activity as measured by aggregometry, flow cytometry, single platelet counting, and the rapid platelet function analyzer.	2001 Oct	11729364
Differential effects of citrate versus PPACK anticoagulation on measured platelet inhibition by abciximab, eptifibatide and tirofiban.	2001 Oct	11729363
[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
A comparison of total hospital costs for percutaneous coronary intervention patients receiving abciximab versus tirofiban.	2001 Oct	11590674
Stability of tirofiban hydrochloride in 0.9% sodium chloride injection for 30 days.	2001 Oct 1	11596703
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
[Comparison of two platelet glycoprotein IIb/IIIa inhibitors, tirofiban and abciximab, for the prevention of ischemic events with percutaneous coronary revascularization].	2001 Sep	11763604
Should patients with unstable coronary syndromes routinely undergo cardiac catheterization and appropriate revascularization?	2001 Sep	11674901
ReoPro rules: results from the 'Do Tirofiban and ReoPro Give Similar Efficacy Trial' (TARGET).	2001 Sep	11585028
Alternatives to unfractionated heparin for anticoagulation in cardiopulmonary bypass.	2001 Sep	11565896
Tirofiban therapy does not increase the risk of hemorrhage after emergency coronary surgery.	2001 Sep	11547328
Adjunctive therapies in the cath lab. Intracoronary tirofiban infusion in a case with massive intracoronary thrombus.	2001 Sep	11533506
An integrated clinical approach to predicting the benefit of tirofiban in non-ST elevation acute coronary syndromes. Application of the TIMI Risk Score for UA/NSTEMI in PRISM-PLUS.	2002 Feb	11792137

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 [WHO-DD]

Common Name

English

TIROFIBAN [VANDF]

Common Name

English

AGRASTAT

Brand Name

English

TIROFIBAN [HSDB]

Common Name

English

TIROFIBAN [INN]

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000008832