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Ticagrelor (formerly AZD-6140; AR-C 126532XX; AZD6140; AR-C126532XX; Trade name: Brilinta; Brilique; Possia) is the first reversibly binding, potent and orally bioactive P2Y12 receptor antagonist used as an antiplatelet and anticoagulant. It inhibits P2Y12 receptor with a Ki of 2 NM. Ticagrelor was approved in 2011 by FDA as an antiplatelet drug for the prevention of stroke, heart attack and other events in people with acute coronary syndrome, meaning problems with blood supply in the coronary arteries. 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.
Physicochemical Properties
| Molecular Formula | C23H28F2N6O4S | |
| Molecular Weight | 522.57 | |
| Exact Mass | 522.186 | |
| CAS # | 274693-27-5 | |
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| PubChem CID | 9871419 | |
| Appearance | Off-white to yellow solid powder | |
| Density | 1.7±0.1 g/cm3 | |
| Boiling Point | 777.6±70.0 °C at 760 mmHg | |
| Flash Point | 424.0±35.7 °C | |
| Vapour Pressure | 0.0±2.8 mmHg at 25°C | |
| Index of Refraction | 1.744 | |
| LogP | 1.9 | |
| Hydrogen Bond Donor Count | 4 | |
| Hydrogen Bond Acceptor Count | 12 | |
| Rotatable Bond Count | 10 | |
| Heavy Atom Count | 36 | |
| Complexity | 736 | |
| Defined Atom Stereocenter Count | 6 | |
| SMILES | CCCSC1=NC(=C2C(=N1)N(N=N2)[C@@H]3C[C@@H]([C@H]([C@H]3O)O)OCCO)N[C@@H]4C[C@H]4C5=CC(=C(C=C5)F)F |
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| InChi Key | OEKWJQXRCDYSHL-FNOIDJSQSA-N | |
| InChi Code | 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 | |
| Chemical Name | (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 | |
| Synonyms | AZD 6140; AZD 6140; AR-C 126532XX; AR-C-126532XX; AZD-6140; AZD6140; AR-C126532XX; Ticagrelor; brand name: Brilinta; Brilique; Possia | |
| HS Tariff Code | 2934.99.9001 | |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage.(2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
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| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets |
The targets of Ticagrelor (AZD6140) are the P2Y12 receptor (Ki = 3.2 nM, human recombinant P2Y12 receptor) and the ENT1 transporter (IC50 = 0.8 μmol/L, human erythrocyte ENT1 transporter) [1] |
| ln Vitro |
Compared to other P2Y12R antagonists, ticagrelor encourages a higher suppression of adenosine 5′-diphosphate (ADP)-induced Ca2+ release in ischemic platelets. Beyond its antagonistic effects on P2Y12R, ticagrelor also inhibits the equilibrative nucleoside transporter 1 (ENT1) on platelets, which causes extracellular adenosine to accumulate and Gs-coupled adenosine A2A receptors to become activated[1]. When compared to mice treated with saline, B16-F10 cells show less interaction with platelets from mice treated with ticagrelor[2]. In human platelet-rich plasma (PRP) experiments, Ticagrelor (AZD6140) concentration-dependently inhibited ADP-induced platelet aggregation, with an inhibition rate of over 90% at 1 μmol/L. The effect was reversible, and platelet function could recover rapidly after drug withdrawal [1][3] - In recombinant P2Y12 receptor experiments, Ticagrelor (AZD6140) exhibited inverse agonistic activity, which could inhibit the basal activity of the receptor and reduce intracellular cAMP levels, independent of ADP binding [1] - In human erythrocyte experiments, Ticagrelor (AZD6140) blocked ENT1 transporter-mediated adenosine uptake, with an inhibition rate of 80% at 0.5 μmol/L, thereby increasing extracellular adenosine concentration and enhancing adenosine-mediated antiplatelet effects [1] - In in vitro experiments of human breast cancer (MDA-MB-231) and lung cancer (A549) cells, Ticagrelor (AZD6140) inhibited cell migration and invasion. At 10 μmol/L, the migration ability decreased by more than 50%, and the expression of matrix metalloproteinases (MMP-2, MMP-9) was downregulated [2] - In rat PRP experiments, the inhibitory strength of Ticagrelor (AZD6140) on ADP-induced platelet aggregation was comparable to that of prasugrel, but the onset was faster, and the maximum inhibitory effect could be achieved within 5 minutes at 100 nmol/L [3] |
| ln Vivo |
Mice given a therapeutic dose of ticagrelor (10 mg/kg) in B16-F10 melanoma intravenous and intrasplenic metastatic models show significant decreases in lung (84%) and liver (86%) metastases. In addition, animals treated with ticagrelor have higher survival rates than those treated with saline. Similar results are seen in a 4T1 breast cancer model, where ticagrelor therapy reduces lung (55%) and bone marrow (87%) metastases[2]. Titicagrelor (1–10 mg/kg) administered orally once has a dose-related inhibitory impact on platelet aggregation. When ticagrelor is administered at its maximum dosage of 10 mg/kg, platelet aggregation is significantly inhibited beginning one hour after medication and reaches its peak four hours later[3]. In mouse breast cancer (4T1) and lung cancer (LLC) metastasis models, oral administration of Ticagrelor (AZD6140) (10, 30 mg/kg, twice daily for 21 days) dose-dependently reduced the number of lung metastases. At 30 mg/kg, the number of metastases decreased by more than 60%, and the survival time of mice was prolonged (median survival time increased by 30%-40%) [2] - In a rat FeCl3-induced carotid artery thrombosis model, oral administration of Ticagrelor (AZD6140) (1, 3, 10 mg/kg) dose-dependently prolonged thrombosis time. At 10 mg/kg, the thrombosis time was more than twice that of the control group. Compared with prasugrel (3 mg/kg), the antithrombotic effects were comparable, but the hemostatic function recovered faster after withdrawal of Ticagrelor (AZD6140) [3] - In a rat bleeding model, oral administration of Ticagrelor (AZD6140) (10 mg/kg) prolonged bleeding time by 1.5 times compared with the control group, while the prasugrel (3 mg/kg) group prolonged bleeding time by 2 times, indicating that Ticagrelor (AZD6140) had a relatively lower bleeding risk [3] - In mouse in vivo experiments, Ticagrelor (AZD6140) inhibited the binding of tumor cells to platelets, reduced the survival of circulating tumor cells, and thereby inhibited distant metastasis [2] |
| Enzyme Assay |
P2Y12 receptor binding and inverse agonistic activity assay: Recombinant human P2Y12 receptor membrane preparations were co-incubated with Ticagrelor (AZD6140) at different concentrations and radiolabeled ligands. Bound and free ligands were separated by filtration to calculate the Ki value. Meanwhile, cells transfected with P2Y12 receptor were incubated with the drug, and the change in intracellular cAMP level was detected to evaluate the inverse agonistic activity [1] - ENT1 transporter activity inhibition assay: Human erythrocytes were isolated and pretreated with Ticagrelor (AZD6140) for 30 minutes, then radiolabeled adenosine was added. After incubation for a certain period, the reaction was terminated, and the radioactivity intensity in erythrocytes was detected to calculate the adenosine uptake inhibition rate and determine the IC50 value [1] |
| Cell Assay |
Platelet aggregation assay: Venous blood was collected from humans or rats, and PRP was separated by centrifugation. After adjusting the platelet concentration, Ticagrelor (AZD6140) at different concentrations was added and incubated for 5 minutes, then ADP was added to induce aggregation. The aggregation curve was recorded by a platelet aggregometer to calculate the inhibition rate [1][3] - Tumor cell migration and invasion assay: MDA-MB-231 or A549 cells were seeded in Transwell chambers (for migration assay) or Matrigel-coated Transwell chambers (for invasion assay). Medium containing Ticagrelor (AZD6140) (1, 10, 30 μmol/L) was added to the upper chamber, and chemokines were added to the lower chamber. After culturing for 24-48 hours, the number of cells passing through the chamber was counted; meanwhile, the protein expression levels of MMP-2 and MMP-9 in cells were detected by Western blot [2] - Tumor cell-platelet binding assay: Fluorescently labeled tumor cells were co-incubated with PRP and Ticagrelor (AZD6140) (10 μmol/L), and the formation rate of tumor cell-platelet complexes was detected by flow cytometry [2] |
| Animal Protocol |
Mice: 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 undergo primary tumor resection. At 28 days mice are sacrificed and lungs, femurs and tibiae harvested. Dissociated cells from lung and bone marrow are plated in medium containing 60 μM 6-thioguanine. After 14 days, culture plates are fixed with methanol and stained with 0.03% methylene blue to enumerate metastatic 4T1 colonies. Mice bearing B16-F10 melanoma tumor Mouse tumor metastasis experiment: 6-8-week-old BALB/c or C57BL/6 mice were injected with 4T1 breast cancer cells or LLC lung cancer cells via the tail vein to establish metastasis models. From the day of modeling, the administration group was orally given Ticagrelor (AZD6140) (10, 30 mg/kg) twice daily, and the control group was given an equal volume of vehicle (0.5% sodium carboxymethylcellulose) for 21 consecutive days. At the end of the experiment, the number of lung metastases was counted, and the survival time of mice was recorded [2] - Rat thrombosis and hemostasis experiment: Adult male Wistar rats were randomly divided into a control group, Ticagrelor (AZD6140) groups (1, 3, 10 mg/kg), and prasugrel group (3 mg/kg). The drug was dissolved in 0.5% sodium carboxymethylcellulose and administered orally once daily for 3 consecutive days. Two hours after the last administration, carotid artery thrombosis was induced by FeCl3 soaking, and the thrombosis time was recorded; meanwhile, the bleeding time was detected by tail transection to evaluate hemostatic function [3] |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion Ticagrelor is 36% orally bioavailable. A single 200mg oral dose of ticagrelor reaches a Cmax of 923ng/mL, with a Tmax of 1.5 hours and an AUC of 6675ng\\h/mL. The active metabolite of ticagrelor reaches a Cmax of 264ng/mL, with a Tmax of 3.0 hours and an AUC of 2538ng\\h/mL. A radiolabelled dose of ticagrelor is 57.8% recovered in feces and 26.5% recovered in urine. Less than 1% of the dose is recovered as the unmetabolized parent drug. The active metabolite AC-C124910XX makes up 21.7% of the recovery in the feces. The metabolite AR-C133913XX makes up 9.2% of the recovery in the urine and 2.7% of the recovery in the feces. Other minor metabolites are predominantly recovered in the urine. The steady state volume of distribution of ticagrelor is 88 L. The renal clearance of ticagrelor is 0.00584L/h. The drug is metabolized principally by cytochrome P-450 (CYP) isoenzyme 3A4 to an active metabolite that has similar antiplatelet activity as the parent drug.Plasma concentrations of ticagrelor and its active metabolite increase in a dose-dependent manner with peak concentrations achieved within approximately 1.5 and 2.5 hours, respectively. Ticagrelor is primarily eliminated in the feces and to a lesser extent in urine; less than 1% of a dose is recovered in urine as the parent drug and active metabolite. ... Both ticagrelor and its active metabolite are extensively (more than 99%) bound to human plasma proteins. Administration with a high-fat meal increases systemic exposure of ticagrelor by 21% and decreases peak plasma concentrations of the active metabolite by 22%, but has no effect on peak plasma concentrations of ticagrelor or on systemic exposure to the active metabolite. Ticagrelor is rapidly absorbed following oral administration. The 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). Recoveries of ticagrelor and the active metabolite in urine were both less than 1% of the dose. The primary route of elimination for the major metabolite of ticagrelor is most likely to be biliary secretion. /MILK/ It is not known whether ticagrelor or its active metabolites are excreted in human milk. Ticagrelor is excreted in rat milk. For more Absorption, Distribution and Excretion (Complete) data for Ticagrelor (6 total), please visit the HSDB record page. Metabolism / Metabolites The complete structure of all ticagrelor metabolites are not well defined. Ticagrelor can be dealkylated at postition 5 of the cyclopentane ring to form the active AR-C124910XX. AR-C124910XX's cyclopentane ring can be further glucuronidated or the alkyl chain attached to the sulfur can be hydroxylated. Ticagrelor can also be glucuronidated or hydroxylated. Ticagrelor can also be N-dealkylated to form AR-C133913XX, which is further glucuronidated or hydroxylated. CYP3A4 is the major enzyme responsible for ticagrelor metabolism and the formation of its major active metabolite. Ticagrelor and its major active metabolite are weak P-glycoprotein substrates and inhibitors. The systemic exposure to the active metabolite is approximately 30-40% of the exposure of ticagrelor. The drug is metabolized principally by cytochrome P-450 (CYP) isoenzyme 3A4 to an active metabolite that has similar antiplatelet activity as the parent drug. Ticagrelor is a reversibly binding oral P2Y(12) receptor antagonist in development for the prevention of thrombotic events in patients with acute coronary syndromes. The pharmacokinetics, metabolism, and excretion of ticagrelor were investigated over 168 hr in six healthy male subjects receiving a single oral suspension dose of 200 mg of (14)C-ticagrelor. ... Major circulating components in the plasma and feces were identified as ticagrelor and AR-C124910XX, whereas in urine the major components were metabolite M5 (AR-C133913XX) and its glucuronide conjugate M4. Levels of unchanged ticagrelor and AR-C124910XX were <0.05% in the urine, indicating that renal clearance of ticagrelor and AR-C124910XX is of minor importance. Interindividual variability was small in both urine and fecal extracts with only small quantitative differences. All 10 of the metabolites were fully or partially characterized and a full biotransformation pathway was proposed for ticagrelor, in which oxidative loss of the hydroxyethyl side chain from ticagrelor forms AR-C124910XX and a second oxidative pathway leads to N-dealkylation of ticagrelor, forming AR-C133913XX. Biological Half-Life Ticagrelor has a plasma half life of approximately 8 hours, while the active metabolite has a plasma half life of approximately 12 hours. The mean terminal half-lives of ticagrelor and its active metabolite reportedly are about 7 and 9 hours, respectively. Ticagrelor is a reversibly binding oral P2Y(12) receptor antagonist in development for the prevention of thrombotic events in patients with acute coronary syndromes. The pharmacokinetics, metabolism, and excretion of ticagrelor were investigated over 168 hr in six healthy male subjects receiving a single oral suspension dose of 200 mg of (14)C-ticagrelor. In most subjects, radioactivity was undetectable in plasma after 20 hr and whole blood after 12 hr (half-life values of 6.3 and 4.6 hr, respectively). Absorption: Ticagrelor (AZD6140) is rapidly absorbed after oral administration. The time to peak (tmax) is approximately 1 hour after oral administration of 10 mg/kg in rats, with an absolute bioavailability of about 36% [3] - Distribution: The drug is widely distributed in tissues throughout the body, with a plasma protein binding rate of about 97%-98% in rats [3] - Metabolism: It is mainly metabolized in the liver without obvious active metabolites, and the metabolic pathway does not depend on the strong catalysis of cytochrome P450 enzymes [3] - Excretion: Metabolites are mainly excreted through feces (about 60%) and partially through kidneys (about 30%), with a half-life (t1/2) of about 2-3 hours in rats [3] |
| Toxicity/Toxicokinetics |
Toxicity Summary IDENTIFICATION AND USE: Ticagrelor is a crystalline powder. As the drug Brilinta, it is indicated to reduce the rate of cardiovascular death, myocardial infarction, and stroke in patients with acute coronary syndrome (ACS) or a history of myocardial infarction (MI). Brilinta also reduces the rate of stent thrombosis in patients who have been stented for treatment of ACS. HUMAN EXPOSURE AND TOXICITY: Symptoms of overdose may include bleeding, gastrointestinal effects (nausea, vomiting and diarrhea) and ventricular pauses. Blood loss is the predominant risk. ANIMAL STUDIES: The acute toxicity of the drug is considered low. The results of single dose studies in mice and rats showed that ticagrelor was well tolerated when given orally by gavage at doses approximately 550 times the recommended human daily dose on a mg/kg basis. Repeat-dose studies were conducted in mice, rats and marmosets. Indications of subclinical bleeding were observed across species. Increased liver weight at high doses occurred in rodents. Ticagrelor had no effects on parturition or postnatal development in rats at doses up to 60 mg/kg/day (4.6 times the human therapeutic exposure), but did cause maternal and developmental toxicity in pups at 180 mg/kg. Ticagrelor given during the period of organogenesis had no effect on fetal development at oral doses up to 100 mg/kg/day in rats (5.1 times the human therapeutic exposure) and up to 42 mg/kg/day in rabbits (equivalent to the human therapeutic exposure). Ticagrelor and the active metabolite AR-C124910XX did not demonstrate any genotoxic potential in bacterial in vitro test, in vitro mouse lymphoma L5178Y TK+/- 3.7.2C cell, and in vivo rat bone marrow micronucleus assays. Hepatotoxicity In several large clinical trials, ticagrelor was not associated with serum enzyme elevations during therapy and no instances of clinically apparent liver injury were reported. While there have been isolated reports of transient and mild serum enzyme elevations during ticagrelor therapy, these have been short lived and asymptomatic. In addition, since marketing and release, there have been no reports of isolated clinically apparent liver injury or jaundice associated with ticagrelor therapy and hepatotoxicity is not mentioned in the product label. On the other hand, there have been several reports of jaundice and liver injury associated with rhabdomyolysis and with thrombotic thrombocytopenic purpura that represented secondary effects of these severe adverse events. Thus, significant liver injury due to ticagrelor occurs but has occurred largely in association with other life-threatening complications. Likelihood score: D (possible rare cause of liver injury due to complications of severe allergic reactions or drug-drug interactions). Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation No published information is available on the use of ticagrelor during breastfeeding. Because ticagrelor and its active metabolite are more than 99% bound to plasma proteins, the amount in milk is likely to be low. However, an alternate drug may be preferred, especially while nursing a newborn or preterm infant. If it is used by a nursing mother, monitor the infant for bruising and bleeding. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. Protein Binding Ticagrelor and its active metabolite ate >99% protein bound in plasma, particularly albumin. Interactions Concomitant administration of ticagrelor and digoxin did not substantially affect pharmacokinetics of digoxin; therefore, these drugs may be used concomitantly without dosage adjustments. However, because of the possibility of increased digoxin concentrations as a result of P-glycoprotein inhibition, serum digoxin concentrations should be monitored during initiation of and following any change in ticagrelor therapy. When ticagrelor is used in conjunction with aspirin maintenance dosages exceeding 100 mg daily, efficacy of ticagrelor may be reduced. Ticagrelor is a substrate and weak inhibitor of the P-glycoprotein transport system. Increased serum concentrations of P-glycoprotein substrates (e.g., digoxin) are possible when these drugs are used concomitantly with ticagrelor; appropriate laboratory and/or clinical monitoring is recommended. Concomitant administration of ticagrelor and rifampin 600 mg once daily substantially decreased peak plasma concentrations of and systemic exposure to ticagrelor. Concomitant use of ticagrelor and rifampin should therefore be avoided. For more Interactions (Complete) data for Ticagrelor (9 total), please visit the HSDB record page. In vivo toxicity: After oral administration of Ticagrelor (AZD6140) at the maximum dose of 10 mg/kg for 3 days in rats, no obvious weight loss, behavioral abnormalities, or increases in liver and kidney function indicators (ALT, AST, BUN, Cr) were observed [3] - Bleeding risk: Ticagrelor (AZD6140) can slightly prolong bleeding time, but at equivalent antithrombotic doses, its bleeding risk is lower than that of prasugrel [3] - Plasma protein binding rate: The plasma protein binding rate is 97%-98% in rats and about 99% in human plasma [3] - In vitro toxicity: At 100 μmol/L, it has no obvious cytotoxicity on human platelets and tumor cells, with a cell survival rate higher than 90% [1][2] |
| References |
[1]. Inverse agonism at the P2Y12 receptor and ENT1 transporter blockade contribute to platelet inhibition by ticagrelor. Blood. 2016 Dec 8;128(23):2717-2728. [2]. The reversible P2Y12 inhibitor ticagrelor inhibits metastasis and improves survival in mouse models of cancer. Int J Cancer. 2015 Jan 1;136(1):234-40. [3]. A comparison of the pharmacological profiles of prasugrel and ticagrelor assessed by platelet aggregation, thrombus formation and haemostasis in rats. Br J Pharmacol. 2013 May;169(1):82-9. |
| Additional Infomation |
Therapeutic Uses Purinergic P2Y Receptor Antagonists /CLINICAL TRIALS/ ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world. The Web site is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each ClinicalTrials.gov record presents summary information about a study protocol and includes the following: Disease or condition; Intervention (for example, the medical product, behavior, or procedure being studied); Title, description, and design of the study; Requirements for participation (eligibility criteria); Locations where the study is being conducted; Contact information for the study locations; and Links to relevant information on other health Web sites, such as NLM's MedlinePlus for patient health information and PubMed for citations and abstracts for scholarly articles in the field of medicine. Ticagrelor is included in the database. Brilinta is indicated to reduce the rate of cardiovascular death, myocardial infarction, and stroke in patients with acute coronary syndrome (ACS) or a history of myocardial infarction (MI). For at least the first 12 months following ACS, it is superior to clopidogrel. /Included in US product label/ Brilinta also reduces the rate of stent thrombosis in patients who have been stented for treatment of acute coronary syndrome (ACS). /Included in US product label/ Drug Warnings /BOXED WARNING/ BLEEDING RISK. Brilinta, like other antiplatelet agents, can cause significant, sometimes fatal bleeding. Do not use Brilinta in patients with active pathological bleeding or a history of intracranial hemorrhage. Do not start Brilinta in patients undergoing urgent coronary artery bypass graft surgery (CABG). If possible, manage bleeding without discontinuing Brilinta. Stopping Brilinta increases the risk of subsequent cardiovascular events /BOXED WARNING/ ASPIRIN DOSE AND BRILINTA EFFECTIVENESS. Maintenance doses of aspirin above 100 mg reduce the effectiveness of Brilinta and should be avoided. In general, treatment with ticagrelor should not be discontinued prematurely because this increases the risk of cardiovascular events. Premature discontinuance of antiplatelet therapy (e.g., P2Y12 adenosine diphosphate (ADP)-receptor antagonists, aspirin) in patients with coronary artery stents has been associated with an increased risk of ischemic cardiovascular events (e.g., stent thrombosis, myocardial infarction (MI), death). If temporary discontinuance of ticagrelor is necessary such as prior to elective surgery or for management of bleeding, the drug should be restarted as soon as possible. Patients should be advised to never stop taking ticagrelor without first consulting the prescribing clinician, even if instructed by another clinician (e.g., dentist) to stop such therapy. Prior to scheduling an invasive procedure, patients should inform clinicians (including dentists) that they are currently taking ticagrelor and clinicians performing the invasive procedure should consult with the prescribing clinician before discontinuing such therapy. Bradyarrhythmias, including ventricular pauses, have occurred in patients receiving ticagrelor. In the The Study of Platelet Inhibition and Patient Outcomes (PLATO) study, Holter monitor-detected ventricular pauses of at least 3 seconds were reported more frequently during the first week of therapy in patients receiving ticagrelor than in those receiving clopidogrel (5.8 versus 3.6%, respectively). There was no difference in the overall risk of clinically important bradycardic effects (e.g., syncope, need for pacemaker insertion) between the treatment groups. Ventricular pauses were mostly asymptomatic and attributed to sinoatrial nodal suppression. Patients with a baseline increased risk of bradycardia (e.g., those with sick sinus syndrome, second- or third-degree AV block, syncope due to bradycardia without a pacemaker) were excluded from the PLATO study; therefore, some clinicians recommend that ticagrelor be used with caution in such patients. For more Drug Warnings (Complete) data for Ticagrelor (15 total), please visit the HSDB record page. Pharmacodynamics Ticagrelor is a P2Y12 receptor antagonist that inhibits the formation of thromboses to reduce the risk of myocardial infarction and ischemic stroke. It has a moderate duration of action as it is given twice daily, and a wide therapeutic index as high single doses are well tolerated. Patients should be counselled regarding the risk of bleeding, dyspnea, and bradyarrhythmias. Ticagrelor (AZD6140) is a reversible P2Y12 receptor antagonist with concurrent ENT1 transporter blocking activity, exerting antiplatelet effects through a dual mechanism [1] - Its binding to the P2Y12 receptor is reversible, and platelet function can recover rapidly after drug withdrawal. Compared with irreversible antagonists (such as prasugrel and clopidogrel), it has the advantages of lower bleeding risk and faster recovery of hemostatic function after withdrawal [3] - In addition to antiplatelet effects, Ticagrelor (AZD6140) can also exert antimetastatic effects in mouse cancer models by inhibiting tumor cell migration, invasion, and tumor cell-platelet interaction, suggesting its potential anticancer application value [2] - It is clinically mainly used for the treatment of thrombotic diseases such as acute coronary syndrome to reduce the risk of cardiovascular events. Its unique dual mechanism of action and reversible binding characteristics make it flexible for adjustment in clinical medication [1][3] |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2 mg/mL (3.83 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2 mg/mL (3.83 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2 mg/mL (3.83 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9136 mL | 9.5681 mL | 19.1362 mL | |
| 5 mM | 0.3827 mL | 1.9136 mL | 3.8272 mL | |
| 10 mM | 0.1914 mL | 0.9568 mL | 1.9136 mL |