| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
APJ[1]
APJ receptor (apelin receptor) is a G protein-coupled receptor that plays important roles in the regulation of cardiovascular function, including cardiac contractility, blood pressure, and angiogenesis. AM-8123 is an APJ agonist that inhibits forskolin-induced cAMP production and promotes Gα protein activation. By activating the APJ receptor, AM-8123 stimulates downstream signaling pathways that lead to improved cardiac function and reduced fibrosis. |
|---|---|
| ln Vitro |
In cells that express APJ, AM-8123 (100 nM) causes β-arrestin to translocate quickly from the cytoplasm to the plasma membrane. AM-8123 exhibited a modest nanomolar affinity for the native hAPJ receptor[1].
In vitro, AM-8123 is an APJ agonist that inhibits forskolin-induced cAMP production and promotes Gα protein activation. It activates APJ receptor signaling. In functional assays, AM-8123 stimulates APJ-mediated signaling pathways, including the activation of G proteins and the inhibition of cAMP production. The compound shows potent agonist activity at the APJ receptor. |
| ln Vivo |
At trial termination, AM-8123 (100 mg/kg; po) reduces both EDV and ESV as determined by echocardiography, but not by the invasive pressure-volume conductance catheter. This leads to a sustained improvement in systolic function[1]. Cardiovascular function is improved by AM-8123 (0.035, 0.09, 0.9, and 9 mg/kg; iv)[1]. In rats and dogs, AM-8123 shows noticeably higher oral bioavailability than pyr-apelin-13. Acute infusion of AM-8123 is linked to improvements in a number of cardiac function indices, as seen by increases in EF, SV, and dP/dt max at submicromolar unbound plasma concentrations with little change in HR. Compared to pyr-apelin-13, AM-8123 is a more effective modulator of both ERK and AKT phosphorylation[1].
In vivo, AM-8123 reduces collagen load, improves cardiac function, and ameliorates myocardial infarction in rats. It shows potential for treating cardiovascular diseases including heart failure. In rat models of myocardial infarction, AM-8123 administration results in reduced infarct size, improved left ventricular function, and decreased cardiac fibrosis. The compound demonstrates cardioprotective effects in preclinical models. |
| Enzyme Assay |
The in vitro enzyme/receptor binding (cell-free) assay for AM-8123 involves binding assays using membrane preparations from cells expressing the APJ receptor to measure the affinity of the compound. Functional assays measuring cAMP accumulation or G-protein activation are used to evaluate agonist activity. Cells expressing APJ receptors are treated with AM-8123, and downstream signaling is measured to determine the potency and efficacy of the compound.
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| Cell Assay |
Cell-based assays using APJ-expressing cells are performed to evaluate the agonist activity of AM-8123. Forskolin-induced cAMP production and Gα protein activation are measured as readouts. Cells are treated with AM-8123, and cAMP levels are measured using ELISA or other detection methods. The agonist activity of the compound is determined by its ability to inhibit cAMP production and activate G proteins.
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| Animal Protocol |
Animal/Disease Models: Lewis rats (2~3 months old)[1]
Doses: 100 mg/kg Route of Administration: Po Experimental Results: Resulted in sustained improvement in systolic function. diminished both EDV and ESV as measured by echocardiography but not by the invasive pressure-volume conductance catheter at study termination. Animal/Disease Models: Rats[1] Doses: 0.035, 0.09, 0.9, and 9 mg/kg Route of Administration: Iv Experimental Results: Improved cardiovascular function. In vivo studies using rat models of myocardial infarction are performed to evaluate the cardioprotective effects of AM-8123. Cardiac function, collagen load, and infarct size are assessed. Rats are subjected to coronary artery ligation to induce myocardial infarction, and AM-8123 is administered orally. Cardiac function is assessed by echocardiography, and infarct size is measured by histochemical staining. |
| ADME/Pharmacokinetics |
AM-8123 is orally bioavailable. It shows good pharmacokinetic properties suitable for in vivo studies. The compound is a nonpeptide APJ agonist, which offers advantages over peptide-based agonists in terms of oral bioavailability and metabolic stability. Further pharmacokinetic studies are needed to fully characterize the ADME properties of AM-8123.
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| Toxicity/Toxicokinetics |
Preclinical toxicology data for AM-8123 are limited. In rat models, the compound shows beneficial effects without reported toxicity. No significant adverse effects have been reported at efficacious doses. Further toxicological evaluation is needed to assess the safety of AM-8123 for potential therapeutic applications.
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| References | |
| Additional Infomation |
AM-8123 (CAS: 2049973-02-4) is a research compound being developed for the treatment of cardiovascular diseases, particularly heart failure. The compound is an orally available nonpeptide APJ agonist. AM-8123 reduces collagen load and improves cardiac function, and ameliorates myocardial infarction in rats. AM-8123 is not approved for human use and is intended for research purposes only. The compound represents a promising lead for the development of APJ agonists for cardiovascular indications.
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| Molecular Formula |
C27H33N7O5S
|
|---|---|
| Molecular Weight |
567.66
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| Exact Mass |
567.226
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| CAS # |
2049973-02-4
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| PubChem CID |
122702584
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| Appearance |
Typically exists as solid at room temperature
|
| LogP |
2.6
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| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
11
|
| Rotatable Bond Count |
11
|
| Heavy Atom Count |
40
|
| Complexity |
873
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| Defined Atom Stereocenter Count |
2
|
| SMILES |
CC1=CC(=CN=C1)C2=NN=C(N2C3=C(C=CC=C3OC)OC)NS(=O)(=O)[C@@H](C)[C@H](C4=NC=C(C=N4)C)OC(C)C
|
| InChi Key |
RKKBDGLXAWMONW-YADARESESA-N
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| InChi Code |
InChI=1S/C27H33N7O5S/c1-16(2)39-24(25-29-13-18(4)14-30-25)19(5)40(35,36)33-27-32-31-26(20-11-17(3)12-28-15-20)34(27)23-21(37-6)9-8-10-22(23)38-7/h8-16,19,24H,1-7H3,(H,32,33)/t19-,24+/m0/s1
|
| Chemical Name |
(1S,2S)-N-[4-(2,6-dimethoxyphenyl)-5-(5-methylpyridin-3-yl)-1,2,4-triazol-3-yl]-1-(5-methylpyrimidin-2-yl)-1-propan-2-yloxypropane-2-sulfonamide
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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) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7616 mL | 8.8081 mL | 17.6162 mL | |
| 5 mM | 0.3523 mL | 1.7616 mL | 3.5232 mL | |
| 10 mM | 0.1762 mL | 0.8808 mL | 1.7616 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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