Identification

Name

Ticagrelor

Accession Number

DB08816

Description

Ticagrelor, or AZD6140, was first described in the literature in 2003.^4,5 Ticagrelor is an ADP derivative developed for its P2Y₁₂ receptor antagonism.⁵ Unlike clopidogrel, ticagrelor is not a prodrug.⁵ It is marketed by Astra Zeneca as Brilinta in the US⁶ and Brilique or Possia in the EU,⁷.

Ticagrelor was granted EMA approval on 3 December 2010.⁷ Ticagrelor was granted FDA approval on 20 July 2011.⁶

Type

Small Molecule

Groups

Approved

Structure

3D

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MOLSDF3D-SDFPDBSMILESInChI

Similar Structures

Structure for Ticagrelor (DB08816)

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Weight

Average: 522.568
Monoisotopic: 522.186080514

Chemical Formula

C₂₃H₂₈F₂N₆O₄S

Synonyms

• (1S,2S,3R,5S)-3-(7-((1R,2S)-2-(3,4-Difluorophenyl)cyclopropylamino)-5-(propylthio)-3H-(1,2,3)triazolo(4,5-d)pyrimidin-3-yl)-5-(2-hydroxyethoxy)cyclopentane-1,2-diol
• Ticagrelor

External IDs

• AR-C126532XX
• AZD 6140
• AZD-6140
• AZD6140

Pharmacology

Indication

Ticagrelor is indicated to reduce the risk of cardiovascular death, myocardial infarction, and stroke in patients with acute coronary syndrome or a history of myocardial infarction.⁶ Ticagrelor is also indicated to reduce the risk of a first myocardial infarction or stroke in high risk patients with coronary artery disease.⁶

Associated Conditions

• Cardiovascular Mortality
• Myocardial Infarction
• Myocardial Infarction First
• Stent Thrombosis
• Stroke

Contraindications & Blackbox Warnings

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Pharmacodynamics

Ticagrelor is a P2Y₁₂ receptor antagonist that inhibits the formation of thromboses to reduce the risk of myocardial infarction and ischemic stroke.^1,3 It has a moderate duration of action as it is given twice daily, and a wide therapeutic index as high single doses are well tolerated.^6,7 Patients should be counselled regarding the risk of bleeding, dyspnea, and bradyarrhythmias.⁶

Mechanism of action

Ticagrelor is a P2Y₁₂ receptor antagonist.¹

The P2Y₁₂ receptor couples with Gα_i2 and other G_i proteins which inhibit adenylyl cyclase.³ G_i mediated signalling also activates PI3K, Akt, Rap1b, and potassium channels.³ The downstream effects of these activities mediate hemostasis and lead to platelet aggregation.³

Antagonism of the P2Y₁₂ receptor reduces development of occlusive thromboses, which can reduce the risk of myocardial infarction and ischemic stroke.³

Target	Actions	Organism
AP2Y purinoceptor 12	inhibitor	Humans

Absorption

Ticagrelor is 36% orally bioavailable.⁶ A single 200mg oral dose of ticagrelor reaches a C_max of 923ng/mL, with a T_max of 1.5 hours and an AUC of 6675ng*h/mL.¹ The active metabolite of ticagrelor reaches a C_max of 264ng/mL, with a T_max of 3.0 hours and an AUC of 2538ng*h/mL.¹

Volume of distribution

The steady state volume of distribution of ticagrelor is 88 L.⁶

Protein binding

Ticagrelor and its active metabolite ate >99% protein bound in plasma, particularly albumin.^2,6

Metabolism

The complete structure of all ticagrelor metabolites are not well defined.¹ Ticagrelor can be dealkylated at postition 5 of the cyclopentane ring to form the active AR-C124910XX.¹ AR-C124910XX's cyclopentane ring can be further glucuronidated or the alkyl chain attached to the sulfur can be hydroxylated.¹ Ticagrelor can also be glucuronidated or hydroxylated.¹ Ticagrelor can also be N-dealkylated to form AR-C133913XX, which is further glucuronidated or hydroxylated.¹

Hover over products below to view reaction partners

• Ticagrelor
  • AR-C124910XX
  • AR-C133913XX

Route of elimination

A radiolabelled dose of ticagrelor is 57.8% recovered in feces and 26.5% recovered in urine.^1,6 Less than 1% of the dose is recovered as the unmetabolized parent drug.⁶ The active metabolite AC-C124910XX makes up 21.7% of the recovery in the feces.¹ The metabolite AR-C133913XX makes up 9.2% of the recovery in the urine and 2.7% of the recovery in the feces.¹ Other minor metabolites are predominantly recovered in the urine.¹

Half-life

Ticagrelor has a plasma half life of approximately 8 hours, while the active metabolite has a plasma half life of approximately 12 hours.¹

Clearance

The renal clearance of ticagrelor is 0.00584L/h.¹

Adverse Effects

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Toxicity

Patients experiencing an overdose may present with bleeding, nausea, vomiting, diarrhea, and ventricular pauses.⁶ Overdose can be managed through symptomatic and supportive treatment, including ECG monitoring.^6,7 Dialysis is not expected to remove ticagrelor from the blood due to it being highly protein bound.⁶

Affected organisms

• Humans and other mammals

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drug	Interaction
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Abametapir	The serum concentration of Ticagrelor can be increased when it is combined with Abametapir.
Abciximab	The risk or severity of bleeding can be increased when Abciximab is combined with Ticagrelor.
Abiraterone	The metabolism of Abiraterone can be decreased when combined with Ticagrelor.
Acalabrutinib	The metabolism of Acalabrutinib can be decreased when combined with Ticagrelor.
Aceclofenac	The risk or severity of bleeding and hemorrhage can be increased when Aceclofenac is combined with Ticagrelor.
Acemetacin	The risk or severity of bleeding and hemorrhage can be increased when Acemetacin is combined with Ticagrelor.
Acenocoumarol	The serum concentration of Acenocoumarol can be increased when it is combined with Ticagrelor.
Acetohexamide	The metabolism of Acetohexamide can be decreased when combined with Ticagrelor.
Acetylsalicylic acid	The therapeutic efficacy of Ticagrelor can be decreased when used in combination with Acetylsalicylic acid.
Afatinib	The serum concentration of Afatinib can be increased when it is combined with Ticagrelor.

Additional Data Available

Extended Description
Extended Description
Extended description of the mechanism of action and particular properties of each drug interaction.
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Severity
Severity
A severity rating for each drug interaction, from minor to major.
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Evidence Level
Evidence Level
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Action
Action
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Food Interactions

• Avoid grapefruit products. Grapefruit inhibits the CYP3A4 metabolism of ticagrelor, which may increase its serum concentration.
• Avoid herbs and supplements with anticoagulant/antiplatelet activity. Herbs with antiplatelet activity may increase the risk of bleeding. Examples include garlic, ginger, bilberry, danshen, piracetam, and ginkgo biloba.
• Avoid St. John's Wort. This herb induces the CYP3A4 metabolism of ticagrelor and may reduce its serum concentration.
• Take with or without food.

Products

Product Images

International/Other Brands

Brilinta / Possia (AstraZeneca)

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
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Brilinta	Tablet	90 mg	Oral	Astra Zeneca	2011-06-01	Not applicable
Brilinta	Tablet	90 mg/1	Oral	AstraZeneca Pharmaceuticals LP	2011-08-05	Not applicable
Brilinta	Tablet	90 mg/1	Oral	bryant ranch prepack	2011-08-05	2016-04-30
Brilinta	Tablet	90 mg/1	Oral	Cardinal Health	2011-08-05	Not applicable
Brilinta	Tablet	60 mg	Oral	Astra Zeneca	2016-06-13	Not applicable
Brilinta	Tablet	60 mg/1	Oral	AstraZeneca Pharmaceuticals LP	2015-09-04	Not applicable
Brilique	Tablet, film coated	60 mg	Oral	Astra Zeneca Ab	2010-12-03	Not applicable
Brilique	Tablet, film coated	60 mg	Oral	Astra Zeneca Ab	2010-12-03	Not applicable
Brilique	Tablet, film coated	90 mg	Oral	Astra Zeneca Ab	2010-12-03	Not applicable
Brilique	Tablet, film coated	90 mg	Oral	Astra Zeneca Ab	2010-12-03	Not applicable

Additional Data Available

Application Number
Application Number
A unique ID assigned by the FDA when a product is submitted for approval by the labeller.
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Product Code
Product Code
A governmentally-recognized ID which uniquely identifies the product within its regulatory market.
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Generic Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
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Na	Tablet	90 mg/1	Oral	Sunshine Lake Pharma Co., Ltd.	2020-04-09	2020-04-10
Na	Tablet	60 mg/1	Oral	Sunshine Lake Pharma Co., Ltd.	2020-04-09	2020-04-10
Ticagrelor	Tablet	90 mg/1	Oral	Amneal Pharmaceuticals NY LLC	2019-01-23	Not applicable

Additional Data Available

Application Number
Application Number
A unique ID assigned by the FDA when a product is submitted for approval by the labeller.
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Product Code
Product Code
A governmentally-recognized ID which uniquely identifies the product within its regulatory market.
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Categories

ATC Codes

B01AC24 — Ticagrelor

• B01AC — Platelet aggregation inhibitors excl. heparin
• B01A — ANTITHROMBOTIC AGENTS
• B01 — ANTITHROMBOTIC AGENTS
• B — BLOOD AND BLOOD FORMING ORGANS

Drug Categories

• Anticoagulants
• Antiplatelet agents
• Blood and Blood Forming Organs
• Carbohydrates
• Cytochrome P-450 CYP2C9 Inhibitors
• Cytochrome P-450 CYP2C9 Inhibitors (weak)
• Cytochrome P-450 CYP3A Inhibitors
• Cytochrome P-450 CYP3A Substrates
• Cytochrome P-450 CYP3A4 Inhibitors
• Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)
• Cytochrome P-450 CYP3A4 Substrates
• Cytochrome P-450 CYP3A5 Inhibitors
• Cytochrome P-450 Enzyme Inhibitors
• Cytochrome P-450 Substrates
• Decreased Platelet Aggregation
• Glycosides
• Hematologic Agents
• Heterocyclic Compounds, Fused-Ring
• Nucleic Acids, Nucleotides, and Nucleosides
• Nucleosides
• P-glycoprotein inhibitors
• P-glycoprotein substrates
• P2Y12 Platelet Inhibitor
• Phenylalanine Hydroxylase Activators
• Platelet Aggregation Inhibitors Excl. Heparin
• Purine Nucleosides
• Purinergic Agents
• Purinergic Antagonists
• Purinergic P2 Receptor Antagonists
• Purinergic P2Y Receptor Antagonists
• Purines
• Ribonucleosides

Chemical TaxonomyProvided by Classyfire

Description

This compound belongs to the class of organic compounds known as triazolopyrimidines. These are polycyclic aromatic compounds containing triazole ring fused to a pyrimidine ring. Triazole is a five-membered ring consisting of two carbon atoms and three nitrogen atoms. Pyrimidine is a 6-membered ring consisting of four carbon atoms and two nitrogen centers at the 1- and 3- ring positions.

Kingdom

Organic compounds

Super Class

Organoheterocyclic compounds

Class

Triazolopyrimidines

Sub Class

Not Available

Direct Parent

Triazolopyrimidines

Alternative Parents

Alkylarylthioethers / Aminopyrimidines and derivatives / Secondary alkylarylamines / Fluorobenzenes / Aryl fluorides / Cyclitols and derivatives / Cyclopentanols / Imidolactams / Triazoles / Heteroaromatic compounds / Dialkyl ethers / Azacyclic compounds / Sulfenyl compounds / Organofluorides / Organopnictogen compounds / Primary alcohols / Hydrocarbon derivatives

show 7 more

Substituents

1,2,3-triazole / Alcohol / Alkylarylthioether / Amine / Aminopyrimidine / Aromatic heteropolycyclic compound / Aryl fluoride / Aryl halide / Aryl thioether / Azacycle / Azole / Benzenoid / Cyclic alcohol / Cyclitol or derivatives / Cyclopentanol / Dialkyl ether / Ether / Fluorobenzene / Halobenzene / Heteroaromatic compound / Hydrocarbon derivative / Imidolactam / Monocyclic benzene moiety / Organic nitrogen compound / Organic oxygen compound / Organofluoride / Organohalogen compound / Organonitrogen compound / Organooxygen compound / Organopnictogen compound / Organosulfur compound / Primary alcohol / Pyrimidine / Secondary alcohol / Secondary aliphatic/aromatic amine / Secondary amine / Sulfenyl compound / Thioether / Triazole / Triazolopyrimidine

show 30 more

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

organofluorine compound, aryl sulfide, secondary amino compound, triazolopyrimidines, hydroxyether (CHEBI:68558)

Chemical Identifiers

UNII

GLH0314RVC

CAS number

274693-27-5

InChI Key

OEKWJQXRCDYSHL-FNOIDJSQSA-N

InChI

InChI=1S/C23H28F2N6O4S/c1-2-7-36-23-27-21(26-15-9-12(15)11-3-4-13(24)14(25)8-11)18-22(28-23)31(30-29-18)16-10-17(35-6-5-32)20(34)19(16)33/h3-4,8,12,15-17,19-20,32-34H,2,5-7,9-10H2,1H3,(H,26,27,28)/t12-,15+,16+,17-,19-,20+/m0/s1

IUPAC Name

(1S,2S,3R,5S)-3-(7-{[(1R,2S)-2-(3,4-difluorophenyl)cyclopropyl]amino}-5-(propylsulfanyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-5-(2-hydroxyethoxy)cyclopentane-1,2-diol

SMILES

CCCSC1=NC2=C(N=NN2[[email protected]@H]2C[[email protected]](OCCO)[[email protected]@H](O)[[email protected]]2O)C(N[[email protected]@H]2C[[email protected]]2C2=CC(F)=C(F)C=C2)=N1

References

Synthesis Reference

Anil Shahaji Khile, "NOVEL PROCESSES FOR THE PREPARATION OF PHENYLCYCLOPROPYLAMINE DERIVATIVES AND USE THEREOF FOR PREPARING TICAGRELOR." U.S. Patent US20130165696, issued June 27, 2013.

US20130165696

General References

1. Teng R, Oliver S, Hayes MA, Butler K: Absorption, distribution, metabolism, and excretion of ticagrelor in healthy subjects. Drug Metab Dispos. 2010 Sep;38(9):1514-21. doi: 10.1124/dmd.110.032250. Epub 2010 Jun 15. [PubMed:20551239]
2. Angheloiu GO, Gugiu GB, Ruse C, Pandey R, Dasari RR, Whatling C: Ticagrelor Removal From Human Blood. JACC Basic Transl Sci. 2017 Apr 24;2(2):135-145. doi: 10.1016/j.jacbts.2017.01.007. eCollection 2017 Apr. [PubMed:30167561]
3. Dorsam RT, Kunapuli SP: Central role of the P2Y12 receptor in platelet activation. J Clin Invest. 2004 Feb;113(3):340-5. doi: 10.1172/JCI20986. [PubMed:14755328]
4. Jacobson KA, Costanzi S, Ohno M, Joshi BV, Besada P, Xu B, Tchilibon S: Molecular recognition at purine and pyrimidine nucleotide (P2) receptors. Curr Top Med Chem. 2004;4(8):805-19. doi: 10.2174/1568026043450961. [PubMed:15078212]
5. Springthorpe B, Bailey A, Barton P, Birkinshaw TN, Bonnert RV, Brown RC, Chapman D, Dixon J, Guile SD, Humphries RG, Hunt SF, Ince F, Ingall AH, Kirk IP, Leeson PD, Leff P, Lewis RJ, Martin BP, McGinnity DF, Mortimore MP, Paine SW, Pairaudeau G, Patel A, Rigby AJ, Riley RJ, Teobald BJ, Tomlinson W, Webborn PJ, Willis PA: From ATP to AZD6140: the discovery of an orally active reversible P2Y12 receptor antagonist for the prevention of thrombosis. Bioorg Med Chem Lett. 2007 Nov 1;17(21):6013-8. Epub 2007 Aug 19. [PubMed:17827008]
6. FDA Approved Drug Products: Brilinta Ticagrelor Oral Tablets [Link]
7. EMA Summary of Product Characteristics: Brilique Ticagrelor Oral Tablet [Link]

External Links

Human Metabolome Database

HMDB0015702

KEGG Drug

D09017

PubChem Compound

9871419

PubChem Substance

175427101

ChemSpider

8047109

BindingDB

50397205

RxNav

1116632

ChEBI

68558

ChEMBL

CHEMBL398435

ZINC

ZINC000028957444

PharmGKB

PA165374673

PDBe Ligand

TIQ

RxList

RxList Drug Page

Drugs.com

Drugs.com Drug Page

Wikipedia

Ticagrelor

AHFS Codes

• 20:12.18 — Platelet Aggregation Inhibitors

PDB Entries

5alb / 5alc

FDA label

Download (1.21 MB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
4	Active Not Recruiting	Not Available	Acute Coronary Syndromes (ACS)	1
4	Active Not Recruiting	Treatment	Acute Coronary Syndromes (ACS)	1
4	Active Not Recruiting	Treatment	Coronary Artery Disease (CAD) / Type 2 Diabetes Mellitus	1
4	Active Not Recruiting	Treatment	LOVASTATIN/TICAGRELOR [VA Drug Interaction]	1
4	Active Not Recruiting	Treatment	Myocardial Infarction	1
4	Active Not Recruiting	Treatment	Non ST Segment Elevation Acute Coronary Syndrome / Non-ST-Elevation Myocardial Infarction / Unstable Angina Pectoris	1
4	Active Not Recruiting	Treatment	Percutaneous Coronary Intervention (PCI)	1
4	Completed	Not Available	Healthy Volunteers	1
4	Completed	Basic Science	Acute Coronary Syndromes (ACS) / Atrial Fibrillation (AF)	1
4	Completed	Basic Science	Coronary Artery Disease (CAD)	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Tablet	Oral	60 mg
Tablet	Oral	90 mg
Tablet, coated		60 mg
Tablet, coated		90 mg
Tablet
Tablet, film coated	Oral	60 mg
Tablet, film coated	Oral	90 mg
Tablet, orally disintegrating	Oral	90 MG
Tablet	Oral	60 mg/1
Tablet, coated	Oral	60 mg
Tablet, coated	Oral	90 mg
Tablet	Oral	90 mg/1

Prices

Not Available

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)	Region
Unlock Additional Data
CA2296665	No	2008-06-10	2018-07-15
CA2351709	No	2010-04-06	2019-12-02
CA2408596	No	2010-12-21	2021-05-31
US7265124	No	2007-09-04	2021-07-09
US6525060	No	2003-02-25	2019-12-02
US7250419	No	2007-07-31	2019-12-02
US6251910	No	2001-06-26	2018-07-15
US8425934	No	2013-04-23	2030-04-17
USRE46276	No	2017-01-17	2019-12-02
US10300065	No	2019-05-28	2036-01-27

Additional Data Available

Filed On
Filed On
The date on which a patent was filed with the relevant government.
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Properties

State

Solid

Experimental Properties

Property	Value	Source
water solubility	10 μg/mL	FDA Label

Predicted Properties

Property	Value	Source
Water Solubility	0.063 mg/mL	ALOGPS
logP	2.31	ALOGPS
logP	2.28	ChemAxon
logS	-3.9	ALOGPS
pKa (Strongest Acidic)	12.94	ChemAxon
pKa (Strongest Basic)	1.11	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	9	ChemAxon
Hydrogen Donor Count	4	ChemAxon
Polar Surface Area	138.44 Å2	ChemAxon
Rotatable Bond Count	10	ChemAxon
Refractivity	142.13 m3·mol-1	ChemAxon
Polarizability	51.31 Å3	ChemAxon
Number of Rings	5	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	No	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Predicted ADMET Features

Property	Value	Probability
Human Intestinal Absorption	+	0.994
Blood Brain Barrier	-	0.6719
Caco-2 permeable	-	0.5989
P-glycoprotein substrate	Substrate	0.7626
P-glycoprotein inhibitor I	Non-inhibitor	0.5907
P-glycoprotein inhibitor II	Non-inhibitor	0.9617
Renal organic cation transporter	Non-inhibitor	0.8606
CYP450 2C9 substrate	Non-substrate	0.7734
CYP450 2D6 substrate	Non-substrate	0.8048
CYP450 3A4 substrate	Substrate	0.5057
CYP450 1A2 substrate	Non-inhibitor	0.5372
CYP450 2C9 inhibitor	Non-inhibitor	0.5767
CYP450 2D6 inhibitor	Non-inhibitor	0.8016
CYP450 2C19 inhibitor	Non-inhibitor	0.6016
CYP450 3A4 inhibitor	Inhibitor	0.8744
CYP450 inhibitory promiscuity	High CYP Inhibitory Promiscuity	0.6243
Ames test	Non AMES toxic	0.5075
Carcinogenicity	Non-carcinogens	0.7777
Biodegradation	Not ready biodegradable	1.0
Rat acute toxicity	2.6308 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.7742
hERG inhibition (predictor II)	Non-inhibitor	0.5914

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	Not Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not Available

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Drug created on August 01, 2011 15:32 / Updated on September 20, 2020 08:50