AM-8123 is an orally bioavailable APJ agonist. AM-8123 inhibits Forskolin-induced cAMP production and promotes Gα protein activation. AM-8123 may be used in cardiovascular disease study.

Physicochemical Properties

Molecular Formula	C27H33N7O5S
Molecular Weight	567.66
Exact Mass	567.226
CAS #	2049973-02-4
PubChem CID	122702584
Appearance	Typically exists as solid at room temperature
LogP	2.6
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	11
Rotatable Bond Count	11
Heavy Atom Count	40
Complexity	873
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
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
HS Tariff Code	2934.99.9001
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)

Biological Activity

Targets	APJ[1]
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].
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].
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.
References	[1]. Cardiovascular response to small-molecule APJ activation. JCI Insight. 2020;5(8):e132898. Published 2020 Apr 23. doi:10.1172/jci.insight.132898.

Solubility Data

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

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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (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.