Ticagrelor-AR-C-126532XX-DataSheet-生命科學試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemETicagrelorCat. No.: HY-10064CAS No.: 274693-27-5Synonyms: AR-C 126532XX; AZD6140分式: CHFNOS分量: 522.57作靶點: P2Y Receptor作通路: GPCR/G Protein儲存式: 4C, protect from light, stored under nitrogen* In solvent : -80C, 6 months; -20C, 1 mon

2、th (protect fromlight, stored under nitrogen)溶解性數(shù)據(jù)體外實驗 DMSO : 50 mg/mL (95.68 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 1.9136 mL 9.5681 mL 19.1362 mL5 mM 0.3827 mL 1.9136 mL 3.8272 mL10 mM 0.1914 mL 0.9568 mL 1.9136 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，

3、并請注意儲備液的保存式和期限。體內(nèi)實驗請根據(jù)您的實驗動物和給藥式選擇適當?shù)娜芙獍?，配制前請先配制澄清的儲備液，再依次添加助溶?為保證實驗結(jié)果的可靠性，體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當天使；澄清的儲備液可以根據(jù)儲存條件，適當保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2 mg/mL (3.83 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubili

4、ty: 2 mg/mL (3.83 mM); Clear solution3. 請依序添加每種溶劑： 10% DMSO 90% corn oil1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemESolubility: 2 mg/mL (3.83 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Ticagrelor (AZD6140)可逆有服活性的 P2Y12 受體拮抗劑，可來治療板聚集。體外研究 Ticagrelor promotes a greater inhibition of adenosine 5-di

5、phosphate (ADP)induced Ca2+ release in ishedplatelets vs other P2Y12R antagonists. This additional effect of ticagrelor beyond P2Y12R antagonism is inpart as a consequence of ticagrelor inhibiting the equilibrative nucleoside transporter 1 (ENT1) on platelets,leading to accumulation of extracellular

6、 adenosine and activation of Gs-coupled adenosine A2A receptors 1.B16-F10 cells exhibit decreased interaction with platelets from ticagrelor-treated mice compared to saline-treated mice 2.體內(nèi)研究 In B16-F10 melanoma intravenous and intrasplenic metastasis models, mice treated with a clinical dose oftic

7、agrelor (10 mg/kg) exhibits marked reductions in lung (84%) and liver (86%) metastases. Furthermore,ticagrelor treatment improves survival compared to saline-treated animals. A similar effect is observed in a4T1 breast cancer model, with reductions in lung (55%) and bone marrow (87%) metastases foll

8、owingticagrelor treatment 2. Single oral administration of ticagrelor (1-10 mg/kg) causes dose-related inhibitoryeffect on platelet aggregation. Ticagrelor, at the highest dose (10 mg/kg) significantly inhibits plateletaggregation at 1 h after dosing and the peak inhibition is observed at 4 h after

9、dosing 3.PROTOCOLAnimal Rats: Prasugrel (10 mg/kg, p.o.) and ticagrelor (30 mg/kg, p.o.), doses that produced similar levels ofAdministration 3 inhibition of platelet aggregation, are administered to rats 4 h before the bleeding time measurements. Fresh,washed platelets (1 1010 platelets/mL) are pre

10、pared from other rats and suspended in Hanks balancedsalt solution. Platelets are transfused via the jugular vein to rats 1 h before the bleeding time measurementsand the bleeding time is determined 3.2Mice: Female BALB/c mice are inoculated subcutaneously in the fourth mammary pad with 4T1 breastca

11、ncer cells. Once a tumor is palpable, mice receive daily injections of PBS or ticagrelor (10 mg/kg). Oneweek later, mice undergo primary tumor resection. At 28 days mice are sacrificed and lungs, femurs andtibiae harvested. Dissociated cells from lung and bone marrow are plated in medium containing

12、60 M 6-thioguanine. After 14 days, culture plates are fixed with methanol and stained with 0.03% methylene blue toenumerate metastatic 4T1 colonies 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Aungraheeta R, et al. Inverse agonism at t

13、he P2Y12 receptor and ENT1 transporter blockade contribute to platelet inhibition byticagrelor. Blood. 2016 Dec 8;128(23):2717-2728.2. Gebremeskel S, et al. The reversible P2Y12 inhibitor ticagrelor inhibits metastasis and improves survival in mouse models of cancer. IntJ Cancer. 2015 Jan 1;136(1):234-40.2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE3. Sugidachi A, et al. A comparison of the pharmacological profiles of prasugrel and ticagrelor assessed by platelet aggregation, thrombusformation and haemostasis in rats. Br J Pharmacol. 2013 May;169(1)