| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 50mg | |||
| 500mg | |||
| Other Sizes |
| Targets |
Azelaprag targets the apelin receptor (APJ), a G protein-coupled receptor involved in cardiovascular regulation and other physiological processes. As an agonist, it activates the receptor, mimicking the effects of endogenous apelin peptides. This activation leads to the inhibition of cAMP production and the promotion of Gα protein activation, which are key downstream signaling events.
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| ln Vitro |
In vitro, Azelaprag has been shown to be a potent agonist of the apelin receptor, with an EC50 of 0.32 nM. It effectively inhibits forskolin-stimulated cAMP production (pEC50=9.64) and promotes Gα protein activation (pEC50=9.54). These activities confirm its efficacy as a small-molecule agonist that can mimic the effects of endogenous peptide ligands.
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| ln Vivo |
In a rescue-impaired renal model, zelaprag (AMG 986) (1 mg/kg/min, rapid intravenous infusion) improves cardiac reserve during dobutamine challenge [2]. Pharmacokinetic parameters of Azelaprag (AMG 986) in rats and dogs [2] Species CL (L/h/kg) VSS (L/kg) T1/2 (h) Oral F(%) Rat 0.78 (dog)[2]. Azelaprag (AMG 986) (0.5/1 mg/kg IV, 1/5 mg/kg wall) demonstrated intravenous T1/2 of 2.4 hours (stent) and 4.2 hours (dog). Wall bioavailability (F %) is 73% (stent) and 97% (dog). Dog 0.08 0.19 4.2 97 0.6 2.4 73
In vivo, Azelaprag (AMG 986) has been evaluated in animal models where it demonstrates cardiovascular effects similar to those of APJ activation. It has shown potential in heart failure research. The compound's ability to activate the apelin receptor in vivo supports its potential therapeutic applications in cardiovascular diseases. |
| Enzyme Assay |
The activity of Azelaprag at the apelin receptor can be assessed using cell-based functional assays. In these assays, cells expressing the apelin receptor are treated with the compound, and downstream signaling is measured. For example, the inhibition of forskolin-stimulated cAMP production is measured using a cAMP assay kit. The EC50 for receptor activation is determined from dose-response curves.
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| Cell Assay |
To evaluate the cellular activity of Azelaprag, cells expressing the apelin receptor are treated with the compound, and Gα protein activation is measured using techniques such as BRET or GTPγS binding assays. The compound's ability to promote Gα protein activation (pEC50=9.54) is quantified. The effects on other downstream signaling pathways can also be assessed.
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| Animal Protocol |
Animal/Disease Models: ZSF1 obese rat (19 weeks old), rat model with impaired metabolic function [2]
Doses: 1 mg/kg/min Route of Administration: acute intravenous (iv) (iv)infusion Experimental Results: Ejection fraction is increased, but not mean arterial pressure, in a rat model of impaired metabolic function. In vivo studies of Azelaprag typically involve animal models of heart failure or other cardiovascular diseases. The compound is administered via oral or intravenous routes, and its effects on cardiac function, blood pressure, and other hemodynamic parameters are measured. The compound's pharmacokinetic profile and tolerability are also assessed in these models. |
| ADME/Pharmacokinetics |
Azelaprag has a molecular weight of 523.61 and is soluble in DMSO (50 mg/mL). It is insoluble in water and ethanol. For in vivo studies, it can be formulated in 5% DMSO, 40% PEG300, 5% Tween 80, and 50% ddH2O, or in 5% DMSO and 95% corn oil.
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| Toxicity/Toxicokinetics |
Specific toxicology data for Azelaprag are not detailed in the available literature. However, as a compound that has been investigated in clinical trials (denoted by the AMG-986 code), it has undergone safety evaluations. In preclinical models, it has been shown to be well-tolerated.
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| References | |
| Additional Infomation |
Azelaprag (AMG-986) is a candidate active molecule being developed as an apelin receptor agonist. It has been investigated for the treatment of cardiovascular diseases, particularly heart failure. Its development represents a successful example of transitioning from peptide signaling to small-molecule activation of the APJ receptor.
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| Molecular Formula |
C25H29N7O4S
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|---|---|
| Molecular Weight |
523.607263326645
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| Exact Mass |
523.2
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| CAS # |
2049980-18-7
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| PubChem CID |
122702529
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| Appearance |
White to light yellow solid powder
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| LogP |
2.7
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
37
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| Complexity |
810
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| Defined Atom Stereocenter Count |
2
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| SMILES |
S([C@H](C)[C@H](C1N=CC(C)=CN=1)C)(NC1=NN=C(C2C=NC=C(C)C=2)N1C1C(=CC=CC=1OC)OC)(=O)=O
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| InChi Key |
DOMQFIFVDIAOOT-QZTJIDSGSA-N
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| InChi Code |
InChI=1S/C25H29N7O4S/c1-15-10-19(14-26-11-15)24-29-30-25(32(24)22-20(35-5)8-7-9-21(22)36-6)31-37(33,34)18(4)17(3)23-27-12-16(2)13-28-23/h7-14,17-18H,1-6H3,(H,30,31)/t17-,18-/m1/s1
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| Chemical Name |
(2R,3S)-N-(4-(2,6-dimethoxyphenyl)-5-(5-methylpyridin-3-yl)-4H-1,2,4-triazol-3-yl)-3-(5-methylpyrimidin-2-yl)butane-2-sulfonamide
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| Synonyms |
MG-986 MG 986 MG986 Azelaprag
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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 : ~5 mg/mL (~9.55 mM)
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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 | 1.9098 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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