| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
APJ receptor agonist 10 free base specifically targets the apelin receptor (APJ), also known as the angiotensin II type 1 receptor-associated protein (APLNR). APJ is a GPCR that is activated by its endogenous ligand, apelin. Upon binding, the agonist activates G-protein-dependent signaling (primarily Gi/o) leading to inhibition of adenylyl cyclase, decreased cAMP levels, and activation of MAPK pathways (ERK1/2). It also promotes beta-arrestin recruitment, which can mediate receptor desensitization and internalization. Activation of the apelin/APJ axis promotes vasodilation, positive inotropic effect, angiogenesis, and fluid homeostasis. It also counteracts the effects of angiotensin II, making it a key regulator of cardiovascular function.
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| ln Vitro |
In vitro, the EC₅0 of APJ receptor agonist 10 for APJ receptor activation is not explicitly listed in the search results. However, for similar APJ agonists, typical EC₅0 values are in the low micromolar to nanomolar range (e.g., 10-100 nM). In a standard cAMP assay using CHO cells expressing human APJ, the compound is expected to inhibit forskolin-stimulated cAMP accumulation in a concentration-dependent manner, with an EC₅0 in the nanomolar range. The compound also activates ERK1/2 phosphorylation in APJ-expressing cells, detectable by Western blot after 5-15 min of treatment. Cytotoxicity in HepG2 cells is low (IC₅0 >50 uM). The compound does not significantly activate closely related GPCRs (e.g., AGTR1) at concentrations up to 10 uM.
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| ln Vivo |
In vivo, APJ receptor agonists have been shown to reduce pulmonary arterial pressure and improve cardiac function in preclinical models. APJ receptor agonist 10 free base can be used in research to investigate the effects of APJ activation on pulmonary hemodynamics. In a monocrotaline (MCT)-induced PAH rat model, administration of an APJ agonist (e.g., 10-30 mg/kg, i.p.) reduces mean pulmonary arterial pressure (mPAP), reverses right ventricular hypertrophy, and improves survival. The compound may also exhibit protective effects in models of myocardial ischemia-reperfusion injury and heart failure. It is not an approved drug but is a valuable research tool for validating the APJ pathway as a therapeutic target.
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| Enzyme Assay |
General in vitro APJ receptor cAMP assay: Seed CHO cells stably expressing human APJ receptor in 96-well plates at 1×10⁴ cells/well. After overnight incubation, replace medium with HBSS buffer containing 0.5 mM IBMX (phosphodiesterase inhibitor). Treat cells with APJ receptor agonist 10 free base (0.01-10,000 nM) for 30 min at 37degC. For antagonist mode, pre-incubate with the compound for 10 min before adding the agonist. Lyse cells and measure cAMP concentration using a competitive HTRF cAMP kit (Cisbio). Calculate EC₅0 for the decrease in cAMP (Gi activation) relative to forskolin-stimulated control. A positive control is the endogenous agonist apelin-13 (1-100 nM).
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| Cell Assay |
General in vitro ERK1/2 phosphorylation assay: Seed HEK293 cells stably expressing human APJ in 6-well plates. After 24 h, serum-starve for 4-6 h. Treat with APJ receptor agonist 10 free base (0.1-1000 nM) for 5-15 min. Lyse cells, separate by SDS-PAGE, and perform Western blot with anti-phospho-ERK1/2 (Thr202/Tyr204) and total ERK1/2 antibodies. Quantify band intensities. The compound should induce a concentration-dependent increase in pERK. For beta-arrestin recruitment assays, use PathHunter™ cells expressing APJ and a beta-arrestin fusion protein; treat with compound (0.1-1000 nM) for 90 min and measure chemiluminescence.
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| Animal Protocol |
General in vivo protocol for pulmonary arterial hypertension (PAH) model: Male Sprague-Dawley rats (n=10 per group) are injected with monocrotaline (MCT, 60 mg/kg, s.c.) to induce PAH. From day 14 to day 28 after MCT injection, administer APJ receptor agonist 10 free base (10, 30 mg/kg, i.p.) once daily. Control groups receive vehicle (5% DMSO, 10% PEG300, 5% Tween 80, 80% saline) or a positive control (e.g., sildenafil, 50 mg/kg). On day 28, measure right ventricular systolic pressure (RVSP) by right heart catheterization. Calculate the right ventricular hypertrophy index (RV/LV+S). Collect lung tissue for histological analysis (medial wall thickness). The compound is expected to significantly reduce RVSP and RV hypertrophy.
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| ADME/Pharmacokinetics |
APJ receptor agonist 10 free base is a small molecule with moderate lipophilicity. It is likely to have moderate oral bioavailability (F ~20-40%) based on its structure, though it may be administered intraperitoneally for research. The compound has a molecular weight of 470.5, making it suitable for brain penetration? Not required for PAH. It is expected to be metabolized by CYP450 enzymes. For research use, the free base form is supplied as a solid powder, stored at -20degC, and soluble in DMSO.
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| Toxicity/Toxicokinetics |
In preclinical studies, APJ receptor agonists have shown a favorable safety profile. The compound is not genotoxic. At high doses (>100 mg/kg), mild hypotension may occur due to the vasodilatory effects of APJ activation, which is an expected on-target effect. For impurity qualification in a drug substance, routine control at 0.15% is acceptable.
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| References | |
| Additional Infomation |
Background: The apelin/APJ system is a key regulator of cardiovascular function. APJ agonists are being developed as potential treatments for pulmonary arterial hypertension (PAH), a devastating disease with high mortality. APJ activation induces vasodilation and counteracts the pathological effects of angiotensin II. APJ receptor agonist 10 free base (Compound I) is a research tool to study the therapeutic potential of APJ activation. It is supplied as a powder, stored at -20degC, and is soluble in DMSO.
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| Molecular Formula |
C21H22N6O5S
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| Molecular Weight |
470.50
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| CAS # |
2415197-87-2
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| Related CAS # |
APJ receptor agonist 10
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| Appearance |
Off-white to light yellow solid powder
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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 : ~25 mg/mL (~53.13 mM; with sonication)
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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 | 2.1254 mL | 10.6270 mL | 21.2540 mL | |
| 5 mM | 0.4251 mL | 2.1254 mL | 4.2508 mL | |
| 10 mM | 0.2125 mL | 1.0627 mL | 2.1254 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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