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Identification
NameTicagrelor
Accession NumberDB08816
TypeSmall Molecule
GroupsApproved
Description

Ticagrelor (trade name Brilinta in the US, Brilique and Possia in the EU) is a platelet aggregation inhibitor produced by AstraZeneca. Unlike clopidogrel, ticagrelor is not a prodrug and does not require metabolic activation. The drug was approved for use in the European Union by the European Commission on December 3, 2010. The drug was approved by the US Food and Drug Administration on July 20, 2011.

Structure
Thumb
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
AZD 6140
AZD-6140
AZD6140
Brilinta
External Identifiers
  • AZD6140
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Brilintatablet60 mg/1oralAstra Zeneca Lp2015-09-04Not applicableUs
Brilintatablet60 mgoralAstrazeneca Canada IncNot applicableNot applicableCanada
Brilintatablet90 mgoralAstrazeneca Canada Inc2011-06-01Not applicableCanada
Brilintatablet90 mg/1oralbryant ranch prepack2011-08-05Not applicableUs
Brilintatablet90 mg/1oralCardinal Health2011-08-05Not applicableUs
Brilintatablet90 mg/1oralAstra Zeneca Lp2011-08-05Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
BriliqueAstraZeneca
PossiaAstraZeneca
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIGLH0314RVC
CAS number274693-27-5
WeightAverage: 522.568
Monoisotopic: 522.186080514
Chemical FormulaC23H28F2N6O4S
InChI KeyInChIKey=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[C@@H]2C[[email protected]](OCCO)[C@@H](O)[[email protected]]2O)C(N[C@@H]2C[[email protected]]2C2=CC(F)=C(F)C=C2)=N1
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassTriazolopyrimidines
Sub ClassNot Available
Direct ParentTriazolopyrimidines
Alternative Parents
Substituents
  • Triazolopyrimidine
  • Alkylarylthioether
  • Secondary aliphatic/aromatic amine
  • Halobenzene
  • Fluorobenzene
  • Aminopyrimidine
  • Imidolactam
  • Benzenoid
  • Pyrimidine
  • Cyclopentanol
  • Monocyclic benzene moiety
  • Aryl halide
  • Aryl fluoride
  • Heteroaromatic compound
  • 1,2,3-triazole
  • Triazole
  • Cyclic alcohol
  • Azole
  • Secondary alcohol
  • 1,2-diol
  • Azacycle
  • Sulfenyl compound
  • Thioether
  • Secondary amine
  • Ether
  • Dialkyl ether
  • Hydrocarbon derivative
  • Primary alcohol
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Organofluoride
  • Organohalogen compound
  • Amine
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationFor the prevention of thrombotic events (for example stroke or heart attack) in patients with acute coronary syndrome or myocardial infarction with ST elevation.
PharmacodynamicsPlasma concentrations of ticagrelor are slightly increased (12–23%) in elderly patients, women, patients of Asian ethnicity, and patients with mild hepatic impairment. They are decreased in patients that described themselves as 'coloured' and such with severe renal impairment. These differences are considered clinically irrelevant. In Japanese people, concentrations are 40% higher than in Caucasians, or 20% after body weight correction. The drug has not been tested in patients with severe hepatic impairment.
Mechanism of actionLike the thienopyridines prasugrel, clopidogrel and ticlopidine, ticagrelor blocks adenosine diphosphate (ADP) receptors of subtype P2Y12. In contrast to the other antiplatelet drugs, ticagrelor has a binding site different from ADP, making it an allosteric antagonist, and the blockage is reversible. Moreover, the drug does not need hepatic activation, which might work better for patients with genetic variants regarding the enzyme CYP2C19 (although it is not certain whether clopidogrel is significantly influenced by such variants).
Related Articles
AbsorptionAbsorbed quickly from the gut, the bioavailability being 36%.
Volume of distribution

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

Protein bindingBoth ticagrelor and AR-C124910XX are bound to plasma proteins (>99.7%), and both are pharmacologically active.
Metabolism

The main metabolite, AR-C124910XX, is formed quickly via CYP3A4 by de-hydroxyethylation at position 5 of the cyclopentane ring. The metabolite reaches 30–40% of ticagrelor's plasma concentrations.

Route of eliminationThe primary route of ticagrelor elimination is hepatic metabolism. When radiolabeled ticagrelor is administered, the mean recovery of radioactivity is approximately 84% (58% in feces, 26% in urine).
Half lifeTicagrelor has a half life of 7 hours, while its active metabolite has a half life of 9 hours.
ClearanceNot Available
ToxicityBleeding is the expected pharmacologic effect of overdosing. If bleeding occurs, appropriate supportive measures should be taken. Other effects of overdose may include gastrointestinal effects (nausea, vomiting, diarrhea) or ventricular pauses.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.994
Blood Brain Barrier-0.6719
Caco-2 permeable-0.5989
P-glycoprotein substrateSubstrate0.7626
P-glycoprotein inhibitor INon-inhibitor0.5907
P-glycoprotein inhibitor IINon-inhibitor0.9617
Renal organic cation transporterNon-inhibitor0.8606
CYP450 2C9 substrateNon-substrate0.7734
CYP450 2D6 substrateNon-substrate0.8048
CYP450 3A4 substrateSubstrate0.5057
CYP450 1A2 substrateNon-inhibitor0.5372
CYP450 2C9 inhibitorNon-inhibitor0.5767
CYP450 2D6 inhibitorNon-inhibitor0.8016
CYP450 2C19 inhibitorNon-inhibitor0.6016
CYP450 3A4 inhibitorInhibitor0.8744
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6243
Ames testNon AMES toxic0.5075
CarcinogenicityNon-carcinogens0.7777
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.6308 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7742
hERG inhibition (predictor II)Non-inhibitor0.5914
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Tabletoral60 mg/1
Tabletoral60 mg
Tabletoral90 mg
Tabletoral90 mg/1
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2296665 No2008-06-102018-07-15Canada
CA2351709 No2010-04-062019-12-02Canada
CA2408596 No2010-12-212021-05-31Canada
US6251910 No1998-07-152018-07-15Us
US6525060 No1999-12-022019-12-02Us
US7250419 No1999-12-022019-12-02Us
US7265124 No2001-07-092021-07-09Us
US8425934 No2010-04-172030-04-17Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
water solubility10 μg/mLFDA Label
Predicted Properties
PropertyValueSource
Water Solubility0.063 mg/mLALOGPS
logP2.31ALOGPS
logP2.28ChemAxon
logS-3.9ALOGPS
pKa (Strongest Acidic)12.94ChemAxon
pKa (Strongest Basic)2.93ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count9ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area138.44 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity142.13 m3·mol-1ChemAxon
Polarizability51.27 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
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 ReferencesNot Available
External Links
ATC CodesB01AC24
AHFS Codes
  • 20:12:18
PDB EntriesNot Available
FDA labelDownload (1.21 MB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AbciximabTicagrelor may increase the anticoagulant activities of Abciximab.
AcenocoumarolTicagrelor may increase the anticoagulant activities of Acenocoumarol.
Acetylsalicylic acidAcetylsalicylic acid may increase the antiplatelet activities of Ticagrelor.
AlteplaseTicagrelor may increase the anticoagulant activities of Alteplase.
AnistreplaseTicagrelor may increase the anticoagulant activities of Anistreplase.
ApixabanThe risk or severity of adverse effects can be increased when Ticagrelor is combined with Apixaban.
AripiprazoleThe serum concentration of Aripiprazole can be increased when it is combined with Ticagrelor.
AtazanavirThe serum concentration of the active metabolites of Ticagrelor can be reduced when Ticagrelor is used in combination with Atazanavir resulting in a loss in efficacy.
AtorvastatinThe serum concentration of Atorvastatin can be increased when it is combined with Ticagrelor.
BexaroteneThe serum concentration of Ticagrelor can be decreased when it is combined with Bexarotene.
BoceprevirThe serum concentration of the active metabolites of Ticagrelor can be reduced when Ticagrelor is used in combination with Boceprevir resulting in a loss in efficacy.
BosentanThe serum concentration of Ticagrelor can be decreased when it is combined with Bosentan.
CarbamazepineThe serum concentration of the active metabolites of Ticagrelor can be reduced when Ticagrelor is used in combination with Carbamazepine resulting in a loss in efficacy.
CarvedilolThe serum concentration of Carvedilol can be increased when it is combined with Ticagrelor.
CeritinibThe serum concentration of the active metabolites of Ticagrelor can be reduced when Ticagrelor is used in combination with Ceritinib resulting in a loss in efficacy.
Citric AcidTicagrelor may increase the anticoagulant activities of Citric Acid.
ClarithromycinThe serum concentration of the active metabolites of Ticagrelor can be reduced when Ticagrelor is used in combination with Clarithromycin resulting in a loss in efficacy.
CobicistatThe serum concentration of the active metabolites of Ticagrelor can be reduced when Ticagrelor is used in combination with Cobicistat resulting in a loss in efficacy.
CollagenaseThe risk or severity of adverse effects can be increased when Ticagrelor is combined with Collagenase.
CyclosporineThe serum concentration of Ticagrelor can be increased when it is combined with Cyclosporine.
Dabigatran etexilateTicagrelor may increase the anticoagulant activities of Dabigatran etexilate.
DabrafenibThe serum concentration of Ticagrelor can be decreased when it is combined with Dabrafenib.
DalteparinTicagrelor may increase the anticoagulant activities of Dalteparin.
DarunavirThe serum concentration of the active metabolites of Ticagrelor can be reduced when Ticagrelor is used in combination with Darunavir resulting in a loss in efficacy.
DasatinibDasatinib may increase the anticoagulant activities of Ticagrelor.
DeferasiroxThe serum concentration of Ticagrelor can be decreased when it is combined with Deferasirox.
Deoxycholic AcidThe risk or severity of adverse effects can be increased when Ticagrelor is combined with Deoxycholic Acid.
DexamethasoneThe serum concentration of the active metabolites of Ticagrelor can be reduced when Ticagrelor is used in combination with Dexamethasone resulting in a loss in efficacy.
DicoumarolTicagrelor may increase the anticoagulant activities of Dicoumarol.
DigoxinThe serum concentration of Digoxin can be increased when it is combined with Ticagrelor.
DofetilideThe serum concentration of Dofetilide can be increased when it is combined with Ticagrelor.
DronabinolThe serum concentration of Dronabinol can be increased when it is combined with Ticagrelor.
Edetic AcidTicagrelor may increase the anticoagulant activities of Edetic Acid.
EnoxaparinTicagrelor may increase the anticoagulant activities of Enoxaparin.
EnzalutamideThe serum concentration of the active metabolites of Ticagrelor can be reduced when Ticagrelor is used in combination with Enzalutamide resulting in a loss in efficacy.
Ethyl biscoumacetateTicagrelor may increase the anticoagulant activities of Ethyl biscoumacetate.
FlibanserinThe serum concentration of Flibanserin can be increased when it is combined with Ticagrelor.
Fondaparinux sodiumTicagrelor may increase the anticoagulant activities of Fondaparinux sodium.
FosphenytoinThe serum concentration of the active metabolites of Ticagrelor can be reduced when Ticagrelor is used in combination with Fosphenytoin resulting in a loss in efficacy.
GlucosamineGlucosamine may increase the antiplatelet activities of Ticagrelor.
HeparinTicagrelor may increase the anticoagulant activities of Heparin.
HydrocodoneThe serum concentration of Hydrocodone can be increased when it is combined with Ticagrelor.
Ibritumomab tiuxetanThe risk or severity of adverse effects can be increased when Ticagrelor is combined with Ibritumomab.
IbrutinibThe risk or severity of adverse effects can be increased when Ibrutinib is combined with Ticagrelor.
IdelalisibThe serum concentration of the active metabolites of Ticagrelor can be reduced when Ticagrelor is used in combination with Idelalisib resulting in a loss in efficacy.
IndinavirThe serum concentration of the active metabolites of Ticagrelor can be reduced when Ticagrelor is used in combination with Indinavir resulting in a loss in efficacy.
ItraconazoleThe serum concentration of the active metabolites of Ticagrelor can be reduced when Ticagrelor is used in combination with Itraconazole resulting in a loss in efficacy.
KetoconazoleThe serum concentration of the active metabolites of Ticagrelor can be reduced when Ticagrelor is used in combination with Ketoconazole resulting in a loss in efficacy.
LimaprostLimaprost may increase the antiplatelet activities of Ticagrelor.
LomitapideThe serum concentration of Lomitapide can be increased when it is combined with Ticagrelor.
LovastatinThe serum concentration of Lovastatin can be increased when it is combined with Ticagrelor.
MitotaneThe serum concentration of the active metabolites of Ticagrelor can be reduced when Ticagrelor is used in combination with Mitotane resulting in a loss in efficacy.
NefazodoneThe serum concentration of the active metabolites of Ticagrelor can be reduced when Ticagrelor is used in combination with Nefazodone resulting in a loss in efficacy.
NelfinavirThe serum concentration of the active metabolites of Ticagrelor can be reduced when Ticagrelor is used in combination with Nelfinavir resulting in a loss in efficacy.
NimodipineThe serum concentration of Nimodipine can be increased when it is combined with Ticagrelor.
ObinutuzumabThe risk or severity of adverse effects can be increased when Ticagrelor is combined with Obinutuzumab.
Omega-3 fatty acidsOmega-3 fatty acids may increase the antiplatelet activities of Ticagrelor.
Pentosan PolysulfateThe risk or severity of adverse effects can be increased when Pentosan Polysulfate is combined with Ticagrelor.
PentoxifyllinePentoxifylline may increase the antiplatelet activities of Ticagrelor.
PhenindioneTicagrelor may increase the anticoagulant activities of Phenindione.
PhenobarbitalThe serum concentration of the active metabolites of Ticagrelor can be reduced when Ticagrelor is used in combination with Phenobarbital resulting in a loss in efficacy.
PhenprocoumonTicagrelor may increase the anticoagulant activities of Phenprocoumon.
PhenytoinThe serum concentration of the active metabolites of Ticagrelor can be reduced when Ticagrelor is used in combination with Phenytoin resulting in a loss in efficacy.
PimozideThe serum concentration of Pimozide can be increased when it is combined with Ticagrelor.
PosaconazoleThe serum concentration of the active metabolites of Ticagrelor can be reduced when Ticagrelor is used in combination with Posaconazole resulting in a loss in efficacy.
PrimidoneThe serum concentration of the active metabolites of Ticagrelor can be reduced when Ticagrelor is used in combination with Primidone resulting in a loss in efficacy.
ReteplaseTicagrelor may increase the anticoagulant activities of Reteplase.
RidogrelTicagrelor may increase the anticoagulant activities of Ridogrel.
RifabutinThe serum concentration of the active metabolites of Ticagrelor can be reduced when Ticagrelor is used in combination with Rifabutin resulting in a loss in efficacy.
RifampicinThe serum concentration of the active metabolites of Ticagrelor can be reduced when Ticagrelor is used in combination with Rifampicin resulting in a loss in efficacy.
RifapentineThe serum concentration of the active metabolites of Ticagrelor can be reduced when Ticagrelor is used in combination with Rifapentine resulting in a loss in efficacy.
RitonavirThe serum concentration of the active metabolites of Ticagrelor can be reduced when Ticagrelor is used in combination with Ritonavir resulting in a loss in efficacy.
RivaroxabanTicagrelor may increase the anticoagulant activities of Rivaroxaban.
SaquinavirThe serum concentration of the active metabolites of Ticagrelor can be reduced when Ticagrelor is used in combination with Saquinavir resulting in a loss in efficacy.
SildenafilThe metabolism of Sildenafil can be decreased when combined with Ticagrelor.
SiltuximabThe serum concentration of Ticagrelor can be decreased when it is combined with Siltuximab.
SimvastatinThe serum concentration of Simvastatin can be increased when it is combined with Ticagrelor.
St. John's WortThe serum concentration of Ticagrelor can be decreased when it is combined with St. John's Wort.
StreptokinaseTicagrelor may increase the anticoagulant activities of Streptokinase.
SulodexideTicagrelor may increase the anticoagulant activities of Sulodexide.
TelaprevirThe serum concentration of the active metabolites of Ticagrelor can be reduced when Ticagrelor is used in combination with Telaprevir resulting in a loss in efficacy.
TelithromycinThe serum concentration of the active metabolites of Ticagrelor can be reduced when Ticagrelor is used in combination with Telithromycin resulting in a loss in efficacy.
TenecteplaseTicagrelor may increase the anticoagulant activities of Tenecteplase.
TipranavirTipranavir may increase the antiplatelet activities of Ticagrelor.
TocilizumabThe serum concentration of Ticagrelor can be decreased when it is combined with Tocilizumab.
TositumomabThe risk or severity of adverse effects can be increased when Ticagrelor is combined with Tositumomab.
TreprostinilTicagrelor may increase the anticoagulant activities of Treprostinil.
UrokinaseTicagrelor may increase the anticoagulant activities of Urokinase.
Vitamin EVitamin E may increase the antiplatelet activities of Ticagrelor.
VoriconazoleThe serum concentration of the active metabolites of Ticagrelor can be reduced when Ticagrelor is used in combination with Voriconazole resulting in a loss in efficacy.
WarfarinTicagrelor may increase the anticoagulant activities of Warfarin.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Guanyl-nucleotide exchange factor activity
Specific Function:
Receptor for ADP and ATP coupled to G-proteins that inhibit the adenylyl cyclase second messenger system. Not activated by UDP and UTP. Required for normal platelet aggregation and blood coagulation.
Gene Name:
P2RY12
Uniprot ID:
Q9H244
Molecular Weight:
39438.355 Da

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
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 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular Weight:
141477.255 Da
Comments
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Drug created on August 01, 2011 15:32 / Updated on July 01, 2016 01:52