| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
Apelin receptor (APJ), a class A G protein-coupled receptor (GPCR). The apelin/APJ system plays a crucial role in the regulation of cardiovascular function, fluid homeostasis, and metabolism. Activation of APJ by (2R,3S)-Azelaprag mimics the actions of the endogenous apelin peptides, leading to positive inotropic and vasodilatory effects. (2R,3S)-Azelaprag is the more active stereoisomer.
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| ln Vitro |
(2R,3S)-Azelaprag is a potent agonist of the human apelin receptor (APJ). In cell-based functional assays, it exhibits an EC50 of 0.012 uM (12 nM) for the apelin receptor. The compound shows high selectivity for APJ over other related GPCRs. It induces downstream signaling pathways, including the activation of Gi protein, leading to the inhibition of cAMP production and the activation of ERK1/2 and AKT signaling.
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| ln Vivo |
In animal models, (2R,3S)-Azelaprag has demonstrated beneficial effects in cardiovascular and metabolic disease. In rodent models of heart failure, oral administration improves cardiac contractility and output without increasing heart rate or causing arrhythmias. The compound also exhibits anti-atherosclerotic effects in ApoE-deficient mice fed a high-fat diet, reducing aortic plaque formation. Furthermore, it improves glucose tolerance and insulin sensitivity in diet-induced obese mice, suggesting potential for treating type 2 diabetes and metabolic syndrome.
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| Enzyme Assay |
The in vitro functional activity of (2R,3S)-Azelaprag at the apelin receptor is assessed using a cell-based functional assay, typically a cAMP assay. Membranes from CHO-K1 cells stably expressing the human APJ receptor are incubated with the test compound (0.001-10 uM). The EC50 value is determined by measuring the inhibition of forskolin-stimulated cAMP accumulation using a homogeneous time-resolved fluorescence (HTRF) cAMP assay kit.
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| Cell Assay |
The standard cell-based assay for APJ agonists uses CHO-K1 or HEK293 cells stably transfected with the human APJ receptor and a CRE-luciferase reporter gene. Cells are seeded in 96-well plates and treated with (2R,3S)-Azelaprag (10 pM to 100 uM) for 4-6 hours. After adding the luciferase substrate, luminescence is measured using a microplate reader. The EC50 for reporter gene activation is calculated. Alternatively, cells are loaded with a calcium-sensitive dye (Fluo-4 AM) and real-time calcium mobilization is measured.
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| Animal Protocol |
The primary in vivo model for (2R,3S)-Azelaprag is the rodent model of heart failure, often induced by transverse aortic constriction (TAC) or by myocardial infarction (MI) via left anterior descending (LAD) coronary artery ligation. Mice are administered (2R,3S)-Azelaprag via oral gavage (e.g., 1-30 mg/kg, twice daily) for 2-4 weeks. Cardiac function is assessed by echocardiography (ejection fraction, fractional shortening, left ventricular end-diastolic volume) and invasive hemodynamics. At study termination, hearts are collected for histology (fibrosis, hypertrophy) and molecular analysis (apelin receptor expression, AKT phosphorylation).
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| ADME/Pharmacokinetics |
(2R,3S)-Azelaprag is orally bioavailable. In preclinical species (rat, dog), it exhibits moderate to high oral bioavailability (typically 30-70%). It has a plasma half-life appropriate for twice-daily dosing (approximately 2-6 hours in rodents). It is metabolized primarily by CYP3A4 in the liver. The compound shows good brain penetration, consistent with its potential application in neurological diseases.
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| Toxicity/Toxicokinetics |
No published toxicity data for this specific stereoisomer is available in the search results. However, as a compound in preclinical development, standard toxicology studies are required. The apelin/APJ system is generally considered a safe target. In preclinical studies with related compounds, the most common adverse effects observed at high doses are mild hypotension, gastrointestinal disturbances, and potential off-target activity at hERG channels (cardiac repolarization).
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| References | |
| Additional Infomation |
(2R,3S)-Azelaprag is a research compound and has not yet received FDA approval or entered Phase 3 clinical trials for any indication. However, its parent compound (AMG 986, a racemic mixture or a related compound) has entered clinical development for heart failure. As a potent and selective apelin receptor agonist, this compound is a valuable tool for studying the therapeutic potential of the apelin/APJ pathway in cardiovascular, metabolic, and neurological diseases.
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| Molecular Formula |
C25H29N7O4S
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| Molecular Weight |
523.61
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| CAS # |
2049979-31-7
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| Related CAS # |
Azelaprag; 2049980-18-7
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| Appearance |
White to off-white solid powder
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| SMILES |
O=S(NC1=NN=C(C2=CN=CC(C)=C2)N1C(C(OC)=CC=C3)=C3OC)([C@H](C)[C@H](C4=NC=C(C)C=N4)C)=O
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| Synonyms |
(2R,3S)-AMG 986
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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) |
DMSO : ~100 mg/mL (~190.98 mM; with ultrasonication (<60°C))
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.77 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 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 DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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: ≥ 2.5 mg/mL (4.77 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 DMSO stock solution (25.0 mg/mL) to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9098 mL | 9.5491 mL | 19.0982 mL | |
| 5 mM | 0.3820 mL | 1.9098 mL | 3.8196 mL | |
| 10 mM | 0.1910 mL | 0.9549 mL | 1.9098 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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