product name Ticagrelor
Description: Ticagrelor, also known as AZD-6140 and AR-C 126532XX, is the first reversibly binding and orally active P2Y12 receptor antagonist with Ki of 2 NM. Ticagreloris was approved in 2011 by FDA. Like 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.
References: J Thromb Haemost. 2009 Sep;7(9):1556-65; Eur J Clin Pharmacol. 2010 May;66(5):487-96.
522.57
Formula
C23H28F2N6O4S
CAS No.
274693-27-5
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 105 mg/mL (200.9 mM)
Water: <1 mg/mL
Ethanol: 53 mg/mL (101.4 mM)
Solubility (In vivo)
Synonyms
AZD 6140
other peoduct :
| In Vitro |
In vitro activity: Ticagrelor is an active drug which, does not require metabolic activation after intestinal absorption. It does not compete directly with ADP at the ADP binding site but occupies an adjacent binding site and acts in an allosteric way, resulting in a reversible conformational change of the receptor. Ticagrelor binds reversibly to the receptor and exhibits rapid onset and offset of effect. Binding studies in rh-P2Y12 receptor-transfected CHO-K1 cells indicate that ticagrelor exhibits potent, rapid, and reversible binding, with a Kd of 10.5 nM, a kon (association constant) of 0.00011/(nM•s), a koff (dissociation constant) of 0.00087/s, and half-life values of 4 min for binding and 14 min for unbinding, indicating that the magnitude of platelet inhibition is dependent on concentrations of drug available to bind platelets. Ticagrelor moderately inhibits CYP2C9 activity in human liver microsomes, while exhibiting little or no inhibition of CYP1A2, CYP2B6, CYP2C8, CYP2C19, CYP2D6, and CYP2E1. In human liver microsomes, ticagrelor inhibits midazolam 4-hydroxylation, while activating 1_-hydroxylation of midazolam. Evaluated in fresh human hepatocytes, ticagrelor is not an inducer of CYP1A2 or CYP3A4. Kinase Assay: Cell Assay: |
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| In Vivo | Absorption of ticagrelor is rapid with t max of 1.3-2 h. And the Cmax and area under the plasma concentration-time curve from time 0 to infinity increases in an apparently dose-proportional manner over the dose range studied, indicating linear pharmacokinetics. The mean terminal-phase half-life (t1/2) is approximately 7-8.5 h for ticagrelor. Inhibition of platelet aggregation (IPA) is dose related and is nearly complete at 2 h at doses of 100-400 mg. Ticagrelor is well tolerated, with no serious or doserelated adverse events or notable changes in laboratory values observed. |
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| References | J Thromb Haemost. 2009 Sep;7(9):1556-65; Eur J Clin Pharmacol. 2010 May;66(5):487-96. |
