| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
Atopaxar hydrobromide targets protease-activated receptor-1 (PAR-1), the primary thrombin receptor on human platelets. It acts as a selective and reversible antagonist with an IC50 of 19 nM. By blocking PAR-1, it inhibits thrombin-induced platelet aggregation.
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|---|---|
| ln Vitro |
The binding of haTRAP (high-affinity thrombin receptor-activating peptide) to PAR-1 on human platelet membranes is inhibited by Atopaxar Hydrobromide (0.0001-10 μM; 1h) in a concentration-dependent manner, with an IC50 of 0.019 μM [2]. Atopaxar Hydrobromide has no effect on platelet aggregation induced by collagen or ADP, but it has a strong inhibitory effect on human platelet aggregation induced by thrombin and TRAP (IC50 of 0.064 and 0.031 μM, respectively) [2]. In guinea pigs, Atopaxar Hydrobromide demonstrated a strong and targeted suppression of thrombin- and TRAP-induced platelet aggregation, with IC50 values of 0.13 and 0.097 μM, correspondingly [2].
In vitro, Atopaxar hydrobromide is a potent PAR-1 antagonist with an IC50 of 19 nM. It shows potent inhibitory effects on human platelet aggregation induced by thrombin. It is a selective and reversible antagonist. |
| ln Vivo |
In a guinea pig model of photochemically induced thrombosis (PIT), atopaxar (30-100 mg/kg; po) hydrobromide causes a dose-dependent extension of femoral artery occlusion time [2]. Even at the highest tested dose of 1000 mg/kg, atopaxa hydrobromide did not cause the guinea pigs' bleeding time to be prolonged [2].
In vivo, Atopaxar hydrobromide is an orally active compound. It has been investigated for the treatment of atherothrombotic disease. It has antiplatelet effects in vivo. Detailed in vivo efficacy data are available from preclinical and clinical studies. |
| Enzyme Assay |
Cell-free PAR-1 receptor binding assays for Atopaxar hydrobromide use membrane preparations from cells expressing human PAR-1. Radioligand binding is performed with a labeled thrombin receptor ligand. The compound is tested at concentrations ranging from 0.1 nM to 100 µM. Non-specific binding is determined using an excess of unlabeled ligand. IC50 and Ki values are calculated from competition curves.
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| Cell Assay |
In vitro cellular assays for Atopaxar hydrobromide use human platelets or cells expressing PAR-1. Platelets are pre-incubated with the compound at concentrations of 0.1-1000 nM for 5-10 minutes. Platelet aggregation is induced by thrombin or PAR-1 agonist peptide and monitored by light transmission aggregometry. The inhibition of aggregation is calculated.
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| Animal Protocol |
Animal/Disease Models: guinea pig, PIT model [2]
Doses: Oral administration Route of Administration: 10 mg/kg, 30 mg/kg, 100 mg/kg Experimental Results: At 30 mg/kg, the occlusion time was prolonged by 1.8 times and 2.4 times compared with Compared with the standard, they are 100 mg/kg and 100 mg/kg respectively. In vivo animal experiments for Atopaxar hydrobromide use rodent or primate models of thrombosis. The compound is administered orally at doses of 0.1-10 mg/kg. Endpoints include occlusion time, thrombus weight, and bleeding time. Platelet aggregation ex vivo is measured to confirm target engagement. Pharmacokinetic parameters are measured in plasma samples. |
| References |
|
| Molecular Weight |
608.5395
|
|---|---|
| Exact Mass |
607.205
|
| CAS # |
474550-69-1
|
| Related CAS # |
Atopaxar;751475-53-3
|
| PubChem CID |
22929978
|
| Appearance |
Typically exists as solid at room temperature
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
10
|
| Heavy Atom Count |
39
|
| Complexity |
817
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
Br[H].FC1C(=C(C([H])=C2C=1/C(=N/[H])/N(C2([H])[H])C([H])([H])C(C1C([H])=C(C(=C(C=1[H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])OC([H])([H])[H])N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H])=O)OC([H])([H])C([H])([H])[H])OC([H])([H])C([H])([H])[H]
|
| InChi Key |
UNMBLVOFOAGGCG-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C29H38FN3O5.BrH/c1-7-37-23-15-19-16-33(28(31)24(19)25(30)27(23)38-8-2)17-22(34)18-13-20(29(3,4)5)26(35-6)21(14-18)32-9-11-36-12-10-32;/h13-15,31H,7-12,16-17H2,1-6H3;1H
|
| Chemical Name |
1-(3-tert-butyl-4-methoxy-5-morpholin-4-ylphenyl)-2-(5,6-diethoxy-4-fluoro-3-imino-1H-isoindol-2-yl)ethanone;hydrobromide
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: Atopaxar hydrobromide (E5555) is prepared in the 0.5% methylcellulose solution[2]. (Please use freshly prepared in vivo formulations for optimal results.)
|
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6433 mL | 8.2164 mL | 16.4328 mL | |
| 5 mM | 0.3287 mL | 1.6433 mL | 3.2866 mL | |
| 10 mM | 0.1643 mL | 0.8216 mL | 1.6433 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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