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

Molecular Formula	C22H36N2O5S
Molecular Weight	440.597
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

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 2760		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 8360	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 1709	substrate 1010	substrate 1193

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP2C19 985 CYP1A2 1032

Drug as victim

Target	Modality	Activity
CYP1A2 1032	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/10534322/ Page: -	no
CYP2C9 1010	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/10534322/ Page: -	no
CYP2C19 985	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/10534322/ Page: -	yes
CYP2D6 1193	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/10534322/ Page: -	yes
CYP3A4 1709	substrate 3326 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
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
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
Cost implications of routine tirofiban use in the management of acute coronary syndromes.	2001 Dec	11744144
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
Glycoprotein IIb/IIIa receptor blockers in acute coronary syndromes.	2001 Dec 8	11747950
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
TACTICS-TIMI 18 shows positive results of invasive approach.	2001 Feb-Mar	11474693
[Update on the treatment with platelet antiaggregation agents].	2001 Jan	11291339
[Update on tirofiban].	2001 Jan 20	11244822
[Tirofiban (Aggrastat). A non-peptide glycoprotein IIb/IIIa receptor inhibitor].	2001 Jan 22	11218789
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
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
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
Effect of Ca2+ chelation on the platelet inhibitory ability of the GPIIb/IIIa antagonists abciximab, eptifibatide and tirofiban.	2001 Mar	11307828
Administration of abciximab to patients receiving tirofiban or eptifibatide: effect on platelet function.	2001 Mar 1	11693761
New approaches to diagnosis and management of unstable angina and non-ST-segment elevation myocardial infarction.	2001 Mar 12	11231699
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
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
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
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
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
Effects of clopidogrel pretreatment before percutaneous coronary intervention in patients treated with glycoprotein IIb/IIIa inhibitors (abciximab or tirofiban).	2001 Oct 15	11676953
Use of coronary revascularization in patients with unstable and non-ST-segment elevation acute myocardial infarction.	2001 Oct 18	11694216
Should patients with unstable coronary syndromes routinely undergo cardiac catheterization and appropriate revascularization?	2001 Sep	11674901
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
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
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

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.

Substance Class	Chemical Created by `admin` on `Thu Jul 06 22:28:43 UTC 2023` Edited by `admin` on `Thu Jul 06 22:28:43 UTC 2023`
Record UNII	GGX234SI5H
Record Status	`Validated (UNII)`
Record Version

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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