Ticagrelor

製品コードS4079 バッチS407903

印刷

化学情報

Chemical Structure Synonyms AZD6140, AR-C 126532XX Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C23H28F2N6O4S
分子量 522.57 CAS No. 274693-27-5
Solubility (25°C)* 体外 DMSO 100 mg/mL (191.36 mM)
Ethanol 100 mg/mL (191.36 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Ticagrelor (AZD6140, AR-C 126532XX) is the first reversibly binding oral P2Y12 receptor antagonist with Ki of 2 nM.
in vitro

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. [1]

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. [3]
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. [2]
特徴 First-in-class of a new type of P2Y12 antagonist known as cyclopentyl-triazolo-pyrimidines.

プロトコル(参考用のみ)

キナーゼアッセイ Binding assays using P2Y12-transfected CHO-K1 or humanplatelet membranes
Membranes (5 μg of protein) are added to a 96-well plate containing [125I]AZ11931285 (125 pM), [3H]ADP (10 nM), or [33P]2MeS-ADP (62.5 pM), the required concentration of competitor, and a sufficient volume of buffer (50 mM Tris, 5 mM MgCl2, 50 mM NaCl, and 0.1% nucleotide-free BSA, pH 7.4) to bring the total volume in each well to 200 μL. Binding studies using platelet membranes and [3H]ADP are performed in the presence of 100 μM (final concentration) MRS2179 to prohibit binding to P2Y1. The signal-to-noise ratios for P2Y12-transfected CHO-K1 cells are approximately 14 for [3H]ADP (specific signal: 895 c.p.m.), 24 for [33P]2MeSADP (specific signal: 3308 c.p.m.), and 24 for [125I]AZ11931285 (specific signal: 3308 c.p.m.). For the studies using platelet membranes, the signal-to-noise ratios are approximately 2 for [33P]2MeS-ADP and [3H]ADP and 1.5 for [125I]AZ11931285, with a specific signal between 100 and 400 c.p.m. In this study, an incubation time of 1 h at 30 癈 is used to allow full equilibrium to be achieved. Thereafter, free radioligand is separated from bound radioligand and counted as described above.
細胞アッセイ 細胞株 BMDMs
濃度 20 μM
反応時間 30 minutes
実験の流れ

Cells were treated with indicated concentration of drug for 30 minutes.
動物実験 動物モデル C57BL/6 mice
投薬量 50 mg/kg
投与方法 i.p.

カスタマーフィードバック

Data from [Data independently produced by , , J Thromb Haemost, 2017, 15(6):1191-1202]

Data from [Data independently produced by , , J Thromb Haemost, 2018, doi:10.1111/jth.14318]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Antiplatelet Activity of Tetramethylpyrazine via Regulation of the P2Y12 Receptor Downstream Signaling Pathway [ Evid Based Complement Alternat Med, 2022, 2022:7941039] PubMed: 35378909
Targeting the P2Y13 Receptor Suppresses IL-33 and HMGB1 Release and Ameliorates Experimental Asthma [ Am J Respir Crit Care Med, 2021, 10.1164/rccm.202009-3686OC] PubMed: 34860143
Ticagrelor Inhibits the NLRP3 Inflammasome to Protect Against Inflammatory Disease Independent of the P2Y 12 Signaling Pathway [ Cell Mol Immunol, 2020, 10] PubMed: 32523112
Antiplatelet Drug Ticagrelor Enhances Chemotherapeutic Efficacy by Targeting the Novel P2Y12-AKT Pathway in Pancreatic Cancer Cells. [ Cancers (Basel), 2020, 12(1)] PubMed: 31968611
The Protease‐Activated Receptor 4 Ala120Thr Variant Alters Platelet Responsiveness to Low‐Dose Thrombin, Protease‐Activated Receptor 4 Desensitization and Is Blocked by Noncompetitive P2Y12 Inhibition [Whitley MJ, et al. J Thromb Haemost, 2018, 10.1111/jth.14318] PubMed: 30347494
Measurement of platelet aggregation, independently of patient platelet count: a flow-cytometric approach. [Vinholt PJ, et al. J Thromb Haemost, 2017, 15(6):1191-1202] PubMed: 28296243
A Platelet/CMC coupled with offline UPLC-QTOF-MS/MS for screening antiplatelet activity components from aqueous extract of Danshen. [Chen Y, et al. J Pharm Biomed Anal, 2016, 117:178-83] PubMed: 26355772
A Platelet/CMC coupled with offline UPLC-QTOF-MS/MS for screening antiplatelet activity components from aqueous extract of Danshen. [Ying Chen, et al. J Pharmaceut Biomed, 2015, 10.1016/j.jpba.2015.06.009]
The importance of sample collection when using single cytokine levels and systemic cytokine profiles as biomarkers-a comparative study of serum versus plasma samples. [Tvedt TH, et al. J Immunol Methods, 2015, 10.1016/j.jim.2015.01.006] PubMed: 25637409

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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