替卡格雷作用機(jī)制 - Medchemexpress - MCE中國

1、Product Data SheetTicagrelorCat. No.: HY-10064CAS No.: 274693-27-5分式: CHFNOS分量: 522.57作靶點(diǎn): 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 month (protect from light, stored undernitrogen)溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 50 mg/mL (95.68 mM)* mea

2、ns soluble, but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration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；旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存式和期限：-80C, 6 months; -20C, 1 month (protect from light, s

3、tored under nitrogen)。-80C 儲存時，請在 6 個內(nèi)使，-20C 儲存時，請在 1 個內(nèi)使。體內(nèi)實(shí)驗(yàn)請根據(jù)您的實(shí)驗(yàn)動物和給藥式選擇適當(dāng)?shù)娜芙獍?。以下溶解案都請先按?In Vitro 式配制澄清的儲備液，再依次添加助溶劑：為保證實(shí)驗(yàn)結(jié)果的可靠性，澄 的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的式助溶1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility

4、: 2 mg/mL (3.83 mM); Clear solution此案可獲得 2 mg/mL (3.83 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 20.0 mg/mL 的澄 DMSO 儲備液加到 400 L PEG300 中，混合均勻；向上述體系中加50 L Tween-80，混合均勻；然后繼續(xù)加 450 L 理鹽定容 1 mL。2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2 mg/mL (3.83 mM); Clear solution此案可獲得 2 mg/mL (3.83 mM

5、，飽和度未知) 的澄清溶液。Page 1 of 2 www.MedChemE以 1 mL 作液為例，取 100 L 20.0 mg/mL 的澄均勻。DMSO 儲備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2 mg/mL (3.83 mM); Clear solution此案可獲得 2 mg/mL (3.83 mM，飽和度未知) 的澄 溶液，此案不適于實(shí)驗(yàn)周 期在半個以上的實(shí)驗(yàn)。以 1 mL 作液為例，取 100 L 20.0 mg/mL 的澄 DMSO 儲備液加到 900 L 油中

6、，混合均勻。BIOLOGICAL 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-diphosphate (ADP)induced Ca2+ release in ished plateletsvs other P2Y12R antagonists. This additional effect of ticagrelor beyond P2Y12R antagonism is in part as a

7、consequence of ticagrelor inhibiting the equilibrative nucleoside transporter 1 (ENT1) on platelets, leading toaccumulation of extracellular adenosine and activation of Gs-coupled adenosine A2A receptors1. B16-F10 cellsexhibit decreased interaction with platelets from ticagrelor-treated mice compare

8、d to saline-treated mice2.體內(nèi)研究 In B16-F10 melanoma intravenous and intrasplenic metastasis models, mice treated with a clinical dose of ticagrelor(10 mg/kg) exhibits marked reductions in lung (84%) and liver (86%) metastases. Furthermore, ticagrelor treatmentimproves survival compared to saline-trea

9、ted animals. A similar effect is observed in a 4T1 breast cancer model, withreductions in lung (55%) and bone marrow (87%) metastases following ticagrelor treatment2. Single oraladministration of ticagrelor (1-10 mg/kg) causes dose-related inhibitory effect on platelet aggregation. Ticagrelor, atthe

10、 highest dose (10 mg/kg) significantly inhibits platelet aggregation at 1 h after dosing and the peak inhibition isobserved at 4 h after dosing3.PROTOCOLAnimal Rats: Prasugrel (10 mg/kg, p.o.) and ticagrelor (30 mg/kg, p.o.), doses that produced similar levels of inhibition ofAdministration 3 platel

11、et aggregation, are administered to rats 4 h before the bleeding time measurements. Fresh, washed platelets (1 1010 platelets/mL) are prepared from other rats and suspended in Hanks balanced salt solution. Platelets aretransfused via the jugular vein to rats 1 h before the bleeding time measurements

12、 and the bleeding time isdetermined3.2Mice: Female BALB/c mice are inoculated subcutaneously in the fourth mammary pad with 4T1 breast cancer cells.Once a tumor is palpable, mice receive daily injections of PBS or ticagrelor (10 mg/kg). One week later, mice undergoprimary tumor resection. At 28 days

13、 mice are sacrificed and lungs, femurs and tibiae harvested. Dissociated cells fromlung and bone marrow are plated in medium containing 60 M 6-thioguanine. After 14 days, culture plates are fixedwith methanol and stained with 0.03% methylene blue to enumerate metastatic 4T1 colonies2.MCE has not ind

14、ependently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Aungraheeta R, et al. Inverse agonism at the P2Y12 receptor and ENT1 transporter blockade contribute to platelet inhibition by ticagrelor. Blood. 2016Dec 8;128(23):2717-2728.2. Gebremeskel S, et al. The reve

15、rsible P2Y12 inhibitor ticagrelor inhibits metastasis and improves survival in mouse models of cancer. Int J Cancer. 2015Page 2 of 3 www.MedChemEJan 1;136(1):234-40.3. Sugidachi A, et al. A comparison of the pharmacological profiles of prasugrel and ticagrelor assessed by platelet aggregation, thrombus formation andhaemostasis in rats. Br J Pharmacol. 2013 May;169(1